From Mist to Medicine: Wound healing Revolution with Liquid Sprays

Heer Trivedi, Isha Bhatt,  Khushi Dolia, Mokshi Rana*, Soumya Bhatt and  Shaileshkumar Koradia

Krishna School of Pharmacy and Research, Drs. Kiran and Pallavi Patel Global University,

Krishna Edu campus, Vadodara-391243, Gujarat, India.

 

*Correspondence: mokshirana22@gmail.com  

DOI: https://doi.org/10.71431/IJRPAS.2026.5210   

Article Information		Abstract
Review Article Received: 03/02/2026 Accepted: 14/02/2026 Published:06/03/2026   Keywords Antimicrobial sprays; Bioadhesive; Protective film; Spray-on Films; Topical Drug   delivery; Transdermals; Wound healing.		Spray bandages are a novel class of topical hemostatic and protective agents designed to foster rapid, non-contact application and conformal coverage of superficial dermal injuries. These formulations typically consist of a hydrophilic polymeric carrier system dissolved or suspended in a volatile solvent, optionally augmented with bioactive agents such as antimicrobials, analgesics, or mitogenic compounds. When sprayed the solvent rapidly evaporates leaving behind a continuous, semi-occlusive polymeric film that adheres to the wound. This film serves as a mechanical barrier against microbial infiltration while preserving a moist wound-healing microenvironment—conditions preferable for epithelial regeneration. Despite several benefits there are challenges regarding standardization, long term safety and economic viability of formulation still exists. This review deals with the preparation and evaluation methods of spray-on bandages, their existing problems and to approaches made to overcome the issue giving outline for future novel drug delivery systems with huge market potential.

 

INTRODUCTION

Wound healing is a dynamic and intricate process shaped by a series of cascades and factors that collectively contribute to wound closure[1]. The success of skin recovery relies on the sequence of events that involve cellular, biochemical, and molecular responses. Consequently, the wound healing process of the extracellular matrix encompasses three overlapping stages: the inflammatory phase, the proliferative phase, and the remodeling phase[2] .These interconnected stages occur in a well-organized manner, overlapping in a cohesive cascade. The promotion of these stages depends on the wound type, its associated pathological conditions, and the condition and type of dressing material. An unusual delay in the wound healing stages can have significant consequences for patients, particularly those with diabetes, venous, or arterial diseases. Other conditions that complicate wound repair include hypotension, hypovolemia, edema, anemia, altered hormonal responses, nutritional deficiencies, and poor hydration. Microbial infections can also delay the wound repair process, ultimately leading to chronic wound infection and recurrence issues[3]. Bacterial proliferation, which results in the colonization of the wound bed, may initiate a subtle immune response that prolongs the inflammatory phase[4] .Consequently, it is essential to develop improved strategies and therapeutic agents to accelerate wound healing[5]. Therefore, it is essential to devise improved strategies and therapeutic agents to accelerate the process of wound healing[6].For those practicing traditional medicine, natural treatments like honey might offer a promising approach to enhance the recovery of various wound types, including surgical wounds, infected surgical wounds, and burns[7]. Recent research indicates that wounds treated with honey tend to heal more rapidly than those left untreated[8]. Additionally, modernization has led to advancements in wound-healing methods, such as the application of medicated film forming spray bandages[9-11] .The advantage of film- forming dosage forms is the ability to improve pharmacokinetics and provide prolonged release in topical therapy[12,13]. The use of aerosol systems for the delivery of film-forming components eliminates the risks of contamination during subsequent storage that remain when using other types of dressings, as well as special devices for application. Spray bandages, also referred to as spray-on or liquid bandages, are topical systems that form a film to offer a sterile, flexible, and non-contact cover for minor injuries, cuts, abrasions, and superficial wounds and scrapes. Usually, these products are kept in aerosol or pump spray systems so that application can be non-contact and uniform onto the wound site. The solvent system evaporates on application, giving rise to a thin, flexible, transparent film that remains fixed on the skin. This idea was first investigated in the mid-20th century to address the medical requirements of soldiers in combat situations, where rapid wound protection and infection control were essential[14].Over time, this technology has advanced to be used in civilian, sports,surgical, and pediatric contexts, providing a convenient alternative to traditional gauze or adhesive bandages[15]. Spray bandages function through a mechanism involving active ingredients like volatile solvent such as ethanol or isopropanol, combined with a film-forming polymer like polyvinylpyrrolidone or ethyl cellulose, and occasionally plasticizers such as PEG or glycerin. When applied, the solvent quickly evaporates, resulting in a thin, clear, and flexible film that sticks to the skin[16,17]. This film serves as a semi-permeable barrier, permitting oxygen to pass through while shielding the wound from bacteria, debris, and physical damage[18].In the case of medicated spray bandages, active pharmaceutical ingredients (APIs) like antibiotics (e.g., mupirocin), antiseptics (e.g., chlorhexidine), or silver nanoparticles are included to provide targeted therapeutic benefits [19,20]. Depending on the purpose for which it is prepared, a spray bandage is considered non-medicated or medicated. For instance, in sports and first aid, one usually prefers to use a fast-drying spray with alcohol for prompt protection, while in post-surgical applications, there is need for prolongation of retention of the film and further antimicrobial activity[21,22].The greatest benefits of spray bandages are: its non-touch application, uniform coverage, adaptability to irregular skin surfaces, and decreased pain and trauma during dressing changes. Sprayable liquid bandage compositions and methods of use.Operating in the commercial sphere, spray bandages have garnered interest in the wound treatment industry owing to the public inclination toward self-medication, quick treatment of wounds, and hygienic dressing options. Furthermore, with innovations through polymer science and nanotechnologies, bioadhesive, biodegradable, and thermoresponsive spray bandages systems were developed, hence an added improvement in clinical performance and user acceptability. This system of delivery is most pertinent to field- or emergency-related situations with the advantage of ease of use, provision of sterile conditions, and rapid wound coverage by aerial spray without the need for direct application or secondary dressing. Spray bandages have been the subject of extensive research and are in use worldwide for first-aid, military medicine, sports injuries, and post-surgical care, wherein biodegradable films, bio-adhesive polymers, and the embedding of nanomaterials are some of the most current innovations to enhance wound healing efficacy. In recent years, there has been a huge commercial interest in spray bandage products due to the rising demand for simple-to-use, over-the-counter wound care solutions[23] . The global advanced wound care sector, such as spray-based technologies, is expected to grow steadily on account of the increasing cases of minor injuries, diabetic ulcers, and surgical wounds[24].

HEALING MECHANISMS

The 4 major phases of wound healing are vascular phase, inflammatory phase, proliferative phase, remodelling phase. The temporal classification of wound healing from seconds after trauma to months or years long is shown in [Fig. 1].

Cellular and molecular pathways in skin healing:

Our skin is specialized to interface with the external environment and provides a variety of important homeostatic functions. Beyond its role in regulating thermostability and sensing extrinsic stimuli, the skin functions as a primary defense barrier that is essential for preserving internal homeostasis. This barrier effectively prevents desiccation and provides protection against a variety of environmental insults, including mechanical trauma, chemical exposure, thermal fluctuations, and photic (particularly ultraviolet) radiation[25]. Integral to this protective function is the skin’s capacity to mount a sophisticated immune barrier response. This immunological interface not only defends against pathogenic invasion but also plays a crucial role in maintaining symbiosis with commensal microorganisms achieved through a finely adapted and tightly regulated host microbiota axis[26]. Importantly when this barrier is compromised the skin rapidly initiates a highly coordinated and efficient set of reparative processes collectively known as the wound healing response[27].

 

Figure 1.  Consecutive or overlapping phases of human skin wound healing from wounding to scarring with description of the most prominent processes and players in each phase.[23]

This response involves multiple overlapping phases having separate biological processes—hemostasis and inflammation, proliferation and remodeling designed to restore the structural and functional integrity of the epidermal barrier as quickly as possible to achieve overall wound healing[28-30]. The body's ability to heal wounds may be hampered by any deficiencies in these phases which collectively constitute the wound healing cascade and any deficiency within these phases may hinder the body's capacity to heal wounds[31].

Haemostasis phase:

Haemostasis is the initial phase of wound healing characterized by the rapid cessation of bleeding through a coordinated sequence of vascular constriction, platelet adhesion and aggregation and activation of the coagulation cascade[32]. This results in the formation of a stable fibrin clot that serves both to prevent blood loss and to provide a provisional matrix for cellular infiltration and tissue repair. It involves complex interactions between endothelial cells, platelets, and plasma-derived coagulation factors[33].

This stage of response begins immediately after occurrence of any injury affecting skin integrity. As blood vessels contract along with activating platelets by coming in contact with exposed collagen making them release their granules resulting in further platelet activation and aggregation. In concurrent with activation of blood clotting cascade this results in deposition of a provisional fibrin scaffold within the wound that supports early wound healing[34].

Upon platelet activation during the hemostatic phase , a spectrum of bioactive mediators including transforming growth factor-β and platelet-derived growth factor are secreted into the wound microenvironment. These cytokines and growth factors act as potent chemoattractants promoting the directed migration and functional activation of neutrophils and monocyte derived macrophages thereby, initiating the cellular and molecular events that characterize the early inflammatory phase of tissue repair[35,36].

Inflammatory phase:

Innate inflammation developed as the initial defense mechanism against pathogenic invasion of wounds. This immune response is launched by injury-induced signals like damage associated molecular patterns from necrotic cells and injured tissue, and pathogen-associated molecular patterns from components of bacteria. These pathogen-associated molecular patterns and damage associated molecular patterns trigger resident immune cells, including mast cells, langerhans cells, T cells and macrophages through binding pattern recognition receptors to trigger downstream inflammatory pathways[37]. Neutrophils are one of the initial cells to be seen acutely [Fig. 2].

Figure 2. Inflammatory phase [37].

Experimental evidence indicates that healing can occur in wounds without neutrophils, in contrast to macrophages, whose function has been shown to be pivotal thus far and in overall healing of the wound[38]. Macrophages which are produced from activated monocytes are engaged in phagocytosis and release of additional cytokines and growth factors that stimulate fibroblast proliferation, angiogenesis and keratinocyte migration. Defective macrophage function in the wound has been correlated with defective wound healing in diabetic wounds[39].

Macrophages also exist in two differentiated subsets according to their gene expression patterns: classically activated and alternatively activated[40] . These macrophages secrete a range of growth factors, such as platelet derived growth factor and vascular endothelial growth factor which are continuously needed to initiate and maintain the development of new tissue at the site of injury. This is attested to by the observation that macrophage-deficient animals are linked to impaired wound healing indicating the pivotal role these cells play in orchestrating the transition from the exudative to the proliferative stage of the tissue repair process[41].

Macrophages carry out the roles of muscular debris phagocytosis, cytokine, and pro-angiogenic, inflammatory, and fibrogenic factor production and secretion, as well as the secretion of free radicals[42]. The macrophage also acts by secreting chemotactic factors and induces other inflammatory cells to migrate to the wound site. Macrophages also secrete prostaglandins which are powerful vasodilators and influence micro-blood vessel permeability. All such factors combined result in the activation of endothelial cells[43]. Such cells also secrete platelet derived growth factor, transforming growth factor-β, fibroblast growth factor and vascular endothelial growth factor which are universally known to be the core cytokines to induce the development of granulation tissue[44].

Proliferative stage:​

The proliferative phase of healing is determined by extensive activation of keratinocytes, fibroblasts, macrophages and endothelial cells to orchestrate wound closure, matrix deposition and angiogenesis[45].This stage is responsible for the repair of the lesion, including angiogenesis, fibroplasia, and re-epithelialization. These events start within the microenvironment of the lesion between the first and the 48th hour and may continue to evolve until the 14th day since the onset of the lesion[46].

The stimulus causes keratinocytes at the wound periphery to undergo a partial epithelial mesenchymal transition, in which they develop an invasive, migratory phenotype[47]. The switch from top-to bottom to front-to-rear polarity allows the lateral migration of leading-edge keratinocytes over the wound, thus the re-growth of the epidermal layer, a process known as re-epithelialization [Fig. 3][48,49]. Keratinocytes at the back of the leading edge re-model their cell adhesion by protein kinase C-α-dependent regulation of desmosome adhesiveness[49] and erythropoietin-producing hepatocellular-dependent regulation of adherens junctions[50], allowing them to re-organize in coordination with advancing epithelial sheet[51]. In addition, keratinocytes of the neo-epidermis secrete matrix metalloproteinases to allow their migratory route, while depositing new extracellular matrix proteins to rebuild the basement membrane[52].

Keratinocyte migration across the wound bed involves navigation through necrotic tissue and cellular debris, mediated by interactions between integrin receptors and structural proteins within the provisional extracellular matrix[53]. Key proteolytic enzymes, notably matrix metalloproteinases-1 and matrix metalloproteinases-9, are essential for this process, as they facilitate the release of integrin-mediated adhesions to enable forward movement[54]. Additional proteases, such as plasmin, contribute to matrix remodeling by degrading fibrin within the wound environment, further supporting keratinocyte migration[55]. Migration halts when keratinocytes from opposing wound margins converge—though the underlying mechanism remains undefined—leading to the formation of a nascent epithelial sheet. Subsequently, keratinocytes establish new matrix adhesions, reassemble the basement membrane, and undergo terminal differentiation to restore the stratified epidermis[56]. Fibroblasts represent the principal cell type responsible for the transition from the initial fibrin-rich provisional matrix to a more structurally organized granulation tissue. Both resident dermal fibroblasts and those of mesenchymal origin respond to a complex array of signaling molecules secreted by platelets, endothelial cells, and macrophages, including transforming growth factor-β and platelet-derived growth factor. These cues guide fibroblasts toward either a pro-fibrotic phenotype—characterized by the synthesis and deposition of extracellular matrix components—or differentiation into myofibroblasts, which mediate wound contraction through enhanced contractile activity[57]. It is increasingly recognized, however, that fibroblasts are not a homogenous population. Functional and developmental heterogeneity among fibroblast subsets contributes to distinct roles during wound repair. In a seminal study[58], identified two embryonically distinct fibroblast lineages in the skin: an upper lineage that promotes re-epithelialization and a lower lineage primarily involved in extracellular matrix production. More recent evidence has further refined this understanding, demonstrating that approximately two-thirds of fibroblasts present in granulation tissue are of myeloid origin, suggesting a significant contribution from wound-derived macrophages[59]. Fibroblasts facilitate matrix remodeling by producing matrix metalloproteinases to degrade the fibrinous provisional matrix and subsequently synthesizing a granulation matrix enriched in fibronectin, immature collagens, and proteoglycans[60]. This granulation tissue functions as a dynamic scaffold that supports the migration and differentiation of various cell types, angiogenesis, and the eventual deposition of mature extracellular matrix components essential for tissue restoration.

The skin contains a complex and densely distributed network of sensory and autonomic nerve fibers that are critical for both sensory perception and motor function. As such, the regeneration of these nerve fibers following injury is essential for functional tissue restoration. Although cutaneous denervation is recognized as a key pathological feature in diabetic wound healing impairment as comprehensively reviewed in [61,62], the role of wound reinnervation itself remains relatively underexplored. Emerging evidence indicates that neuropeptides released from both regenerating nerve endings and immune cells during tissue repair, modulate a variety of cellular responses including proliferation and angiogenesis[63]. Importantly, levels of neuropeptides are markedly diminished in chronic diabetic wounds, and exogenous application has been shown to not only enhance wound healing outcomes[64,65], but also promote peripheral nerve regeneration[66]. Additionally, glial cells activated during cutaneous injury contribute to the repair milieu by expressing chemotactic and reparative factors; conversely, their depletion has been associated with delayed wound closure in murine models[67]. Collectively, these findings underscore a critical, yet underappreciated, role for the peripheral nervous system and its cellular components in orchestrating effective wound healing.

Figure 3. Proliferative phase [48,49].

Matrix remodeling:

The remodeling phase of wound healing typically commences two to three weeks following injury and may extend for a year or longer. This final phase is primarily aimed at restoring maximal tensile strength to the tissue through dynamic processes involving the reorganization, degradation, and re-synthesis of the extracellular matrix. During this stage, granulation tissue undergoes progressive remodeling, resulting in the formation of scar tissue characterized by reduced cellularity and vascularity[68], alongside a gradual enrichment in collagen content. Notably, this phase involves the maturation of wound components and the resolution of the initial inflammatory response, accompanied by significant alterations in the extracellular matrix architecture.

Re-epithelialization culminates when a keratinocyte monolayer covers the wound surface, halting further epidermal migration[69]. Subsequently, a stratified epidermis and a newly formed basal lamina are re-established from the wound margins inward[70]. Matrix deposition continues during this phase, accompanied by compositional changes. Type III collagen, which predominates in earlier stages, is progressively degraded, while type I collagen synthesis is upregulated. Additionally, levels of hyaluronic acid and fibronectin decline, primarily due to degradation mediated by cellular and plasma-derived metalloproteinases. These molecular and structural transformations collectively contribute to the restoration of tissue integrity and function[71].

In the final stage of wound healing, collagen fibers undergo structural reorganization, becoming thicker and more aligned in parallel bundles, thereby enhancing the tensile strength of the repaired tissue[72]. This resolution phase is critical for restoring both the functional capacity and morphological appearance of the injured tissue[73]. The reduction in chemokine production—primarily driven by anti-inflammatory cytokines such as interleukin-10 and transforming growth factor-beta 1 —is central to this process. Collagen synthesis is regulated by several growth factors, including transforming growth factor-beta 1 and fibroblast growth factor, which significantly influence the transcription of extracellular matrix-associated genes.

During maturation and remodeling, the majority of blood vessels, fibroblasts, and inflammatory cells are eliminated from the wound area through apoptosis, emigration, or other poorly understood mechanisms of cell death, leading to a hypocellular scar[74,75]. Concurrently, fibroblasts undergo phenotypic conversion into myofibroblasts, characterized by the temporary expression of α-smooth muscle actin.

These myofibroblasts acquire contractile properties akin to smooth muscle cells, migrate toward the wound edges, and are principally responsible for wound contraction. They exhibit well-organized actin microfilament bundles, which are interconnected via gap junctions and anchored to the extracellular matrix through integrin receptors. These receptors specifically bind to fibronectin, as well as type I and III collagen, facilitating the mechanical remodeling of the wound environment[76]. Notably, myofibroblasts are major extracellular matrix-producing cells in fibrotic processes[77].

The extracellular matrix plays an active, regulatory role during this stage by interacting with structural proteins and cellular components within the tissue. Key extracellular matrix constituents such as collagen, fibronectin, and fibrin initiate signaling events that influence cell adhesion, migration, and behavior. For example, fibronectin forms a scaffold that supports cellular migration, while vitronectin contributes to tissue contraction by facilitating fibroblast-mediated collagen interactions.

Given the complexity of these interactions, modulating cell–extracellular matrix  dynamics has emerged as a promising therapeutic target in wound management.

It is also essential to highlight that both endogenous and exogenous factors significantly affect the healing trajectory. Systemic disorders such as diabetes mellitus, immunosuppression, and venous insufficiency, along with external influences like corticosteroid therapy and smoking, can delay wound closure. Furthermore, complications such as hypertrophic scarring and keloid formation may arise during or after the remodeling process[78].

TYPES OF APPLICATORS USED IN SPRAY BANDAGES:

Spray bandage systems are designed to deliver a thin, protective film over wounds, offering benefits such as ease of use, sterility, and rapid application. The effectiveness of such systems heavily depends on the type of applicator used. Applicators can be broadly categorized based on their mode of propulsion and atomization technology. A comparative study of different types of applicators is shown in Table 1.

Aerosol-Based Applicators:

These utilize pressurized containers with propellants (typically hydrocarbons or compressed gases) to deliver the bandage formulation as a fine mist or spray. Aerosol systems enable uniform deposition over irregular wound surfaces and are commonly used due to ease of application and rapid film formation. However, formulation compatibility with propellants and environmental concerns regarding volatile organic compounds are notable limitations.

Aerosol spray bandage systems consist of a pressurized metal or plastic container fitted with a valve and actuator mechanism, containing a mixture of a film-forming polymer, solvent (commonly alcohol), and a propellant. These systems offer several advantages, including uniform and consistent spray distribution, rapid and efficient film formation, easy single-handed application, and high portability with a long shelf life. However, they also present certain limitations such as the potential flammability and toxicity of propellants, environmental concerns related to VOC emissions and greenhouse gases, pressure-related restrictions in clinical settings (especially oxygen-rich environments), and the need for formulation stability under pressurized conditions. Aerosol technology is widely used in commercially available spray bandages, including products such as 3M Nexcare and Elastoplast Spray Bandage.[79].

Pump-Based (Non-Aerosol) Applicators:

These systems employ mechanical pumps to atomize the formulation without the need for propellants. They are often used for water-based or alcohol-based polymer solutions. Pump spray applicators offer greater formulation flexibility and environmental safety but may deliver less uniform coverage compared to aerosol systems.

Pump spray systems comprise a pump actuator with a dip-tube, an adjustable or fixed nozzle, and formulations based on aqueous or alcohol-based polymer solutions. These systems are considered safer and more environmentally friendly as they do not rely on pressurized propellants, and they offer greater flexibility for incorporating thermolabile or biologically active components while being compatible with a wider range of viscosities and solvents. However, pump sprays may produce larger droplet sizes with less uniform coverage, require greater manual effort during application, and are limited in their ability to generate very fine, mist-like sprays. Owing to these characteristics, pump spray technology is commonly used in medical and cosmetic applications where safety and formulation flexibility are key priorities[80].

Electrohydrodynamic and Electrospray Applicators:

These advanced systems use electrical forces to atomize and deposit polymer solutions at the wound site. While still largely experimental, they allow for precise control over droplet size and deposition, making them suitable for delivering bioactive agents or nanoparticles with the film-forming matrix.

This approach offers extremely fine control over droplet size and spray pattern, making it well suited for delivering heat-sensitive and bioactive compounds such as peptides, antibiotics, and growth factors. It also allows the incorporation of nanoparticles, liposomes, or nanofibers to achieve controlled drug release, which is particularly valuable in advanced wound healing strategies. However, the equipment required is expensive and technically complex, and its use in wound care remains largely at the preclinical or experimental stage, limiting suitability for routine clinical practice or home use. As a result, its primary applications are currently in research settings, especially for the delivery of therapeutic agents in advanced wound dressings and tissue engineering applications[81].

Compressed Gas Jet Systems:

These applicators rely on external compressed air or carbon dioxide sources to generate a fine spray. They are typically used in clinical or field settings where pressurized canisters are not ideal. These systems allow high control over spray velocity and direction but require bulky equipment.

This method is non-flammable and safe for use in clinical environments, making it suitable for larger or deeper wounds where higher delivery pressures are required. Because it does not rely on chemical propellants, it is more environmentally friendly. However, it requires an external gas source, which makes the system bulkier and less portable, and the associated equipment costs and maintenance requirements can be relatively high. These factors also make it less practical for over-the-counter products. Consequently, it is mainly used in hospital or field settings where precise delivery and safety are critical[82].

Selection Criteria for Applicators

Choice of applicator depends on several factors like - formulation properties (viscosity, volatility, polymer type), desired spray characteristics (droplet size, coverage, film thickness), clinical context (home use vs. surgical use), regulatory and safety constraints, target patient population and wound type.

Comparative Summary:

Refer Table 1. Comparative summary of the different types of Spray bandages:

Table 1. Comparative summary of the different types of Spray bandages

 

CLASSIFICATION

Based on Container types:

Conventional Spray: This system utilizes standard plastic or aluminium containers fitted with a dip tube of approximately 1.2 mm and an aperture size of about 0.3 mm. It produces a spray angle ranging from roughly 78.7° to 87.4° and delivers 0.11–0.35 g/mL per actuation, with very low leakage rates of 0.01–0.03%. The device can be operated in either vertical or horizontal orientations, and the 3 K® Level Spray Nozzle has been reported to maintain formulation sterility during both storage and use. Spray performance is influenced by polymer type and concentration, and ordinal spray configurations can be applied for formulations containing botanical extracts[83].

Metered-Dose Spray (MDS): This system delivers a precise and consistent volume per actuation, which is critical for controlled dosing in transdermal and transmucosal delivery. Typical spray volumes range from 90 to 102 mL with a spray angle of approximately 83.5°, and leakage rates remain low at about 0.01–0.02%. Spray performance is influenced by factors such as container volume, dispersion uniformity, and the orientation of the device during application[84].

Electrostatic Spray: This approach enhances deposition efficiency, accelerates droplet formation, improves spray uniformity, and reduces drift in film formation systems. Optimal performance is achieved with solution conductivities in the range of 10⁵–10⁸ S/m, producing droplet sizes typically between 4 and 26 µm, with an average of about 6–12 µm. It is particularly effective at improving film coverage and uniformity when working with viscous or electrically charged polymer systems[85].

Ultrasonic Spray: This technique produces homogeneous nanoscale droplets smaller than 10 µm using a 0.5 mm nozzle operating at a resonance frequency of approximately 10MHz. It enables precise layer-by-layer film formation with a narrow particle size distribution, making it well suited for clinical applications that require accurate coating control. Droplet size is influenced by factors such as solution viscosity, surface tension, and the applied vibration frequency[86].

Based on Application Purpose

Skin Protectants: Over-the-counter sprays or gels are commonly used for minor superficial wounds such as small cuts, scrapes, or sores, where they form a temporary polymer layer that protects and isolates the wound while still allowing gas exchange. In addition, cyanoacrylate-based liquid skin protectants have been highlighted in review literature for their effectiveness in treating conditions such as pedal fissures and minor wounds, providing comfort, ease of application, and disease protection comparable to more complex wound dressings[87].

Suture Replacements: In clinical settings, polymeric tissue adhesives such as 2-octyl cyanoacrylate are used by healthcare professionals to close serious lacerations and surgical incisions. Review studies report superior cosmetic outcomes, comparable or faster wound closure times compared with sutures, a reduced risk of infection, and the added advantage of eliminating the need for suture removal[88,89].

Based on Film-Forming Characteristics :

Dense Film-Forming Systems These systems form hard, durable films that function similarly to bandages or sponge-like coatings, creating a mechanical barrier against external contaminants. They are well suited for providing structural protection and cushioning, and some formulations also enable exudate absorption. Common examples include polymer-thickened systems or high-viscosity gels that dry after application to form stiff, rigid coverings[90].

 Plastic Film-Forming Systems:These systems form elastic, semi-flexible films, often utilizing biopolymers such as alginate, chitosan, or gelatin. They support controlled drug release, help maintain moisture balance, and promote faster re-epithelialization of wounds. Their combination of elasticity and moderate density makes them particularly well suited for application on mobile skin areas, such as joints or folds[91].

Soft Film-Forming Systems: These systems produce thin, highly adhesive films that are lightweight and flexible, intended for short-term protection of minor wounds. Their strong adhesiveness enables them to remain securely in place, even on areas with frequent movement such as the knees or elbows. They are commonly used for minor abrasions, cuts, or skin irritations, providing rapid protection while allowing for minimal restriction of movement[92].

Based on Formulation Type and Clinical Application:

 Film-Forming Liquid Bandages: These spray systems use polymers (e.g., cellulose derivatives, acrylates) that form transparent, flexible film upon solvent evaporation, sealing minor cuts and abrasions. They are breathable, waterproof, and reduce contamination[93]. A systematic Bentham review emphasizes their flexibility, rapid drying time, and capacity to serve as controlled drug-delivery vehicles in wound care[94]. While ideal for small superficial wounds, they may hinder healing in larger wounds due to non-absorbent nature[95].

 Cyanoacrylate-Based Medical Sprays: These use alkyl cyanoacrylates (butyl, octyl) as tissue adhesives. Butyl & octyl variants cause less inflammation compared to methyl/ethyl types, and degrade more slowly, enhancing healing. Octyl-2-cyanoacrylate sprays have shown faster epithelialization, complete haemostasis, and reduced scabbing in animal models versus conventional dressings[96]. Clinical use accelerates wound closure in surgical settings, reduces operation time, and offers tensile strength comparable to sutures after 5–7 days[97].

Antiseptic Spray Bandages: These combine film-forming polymers with antimicrobial agents (e.g., benzalkonium chloride, iodine). While widely used in consumer products, there is limited dedicated peer-reviewed research isolating their efficacy. However, liquid bandages containing antiseptics show comparable barrier function to non-antiseptic variants, supporting infection control in first-aid settings . Further clinical trials would strengthen evidence for their added benefit.

Advanced/Bio-active Gel-Forming Sprays:  Emerging gelatin-polyethylene glycol and chitosan-based sprays rapidly gel into bio adhesive films that can include antimicrobial or growth factors[98].

Veterinary Spray Bandages: Veterinary spray bandages are specialized topical formulations designed for use in animals, offering a no-touch, quick-drying protective film over wounds such as abrasions, surgical sites, and minor lacerations. These sprays typically contain film-forming agents like micronized aluminium or zinc oxide, often combined with antiseptics such as gentian violet or acriflavine, providing both a physical barrier and antimicrobial activity . The formulations are water-resistant, breathable, and designed to adhere to fur or skin even in outdoor environments, making them ideal for livestock and companion animals where traditional dressings are impractical. Products like Aluspray® and Blue Kote® are widely used for post-procedural care, including dehorning, tail docking, and minor injuries, with added colorants for visual confirmation of application[99,100].

 COMPARISON BETWEEN CONVENTIONAL BANDAGES & SPRAY BANDAGES

Adhesion & Tissue Trauma

Self-adhesive bandages, such as those using silicone, hydrocolloid, or acrylic adhesives, vary in their effects on the skin. Soft silicone adhesives are associated with significantly less skin stripping and discomfort compared to acrylic or hydrocolloid options, whereas hydrocolloid dressings can remove the stratum corneum and cause pain. In contrast, sprayable polymer dressings, such as PLGA/PEG blends, can be applied using a no-touch spray technique, minimizing disturbance to the wound bed and reducing the risk of microbial transmission. These biodegradable dressings form an adhesive scaffold that can be removed with minimal trauma[101,102].

Moist Healing Environment & Regeneration

Self-adhesive dressings, including hydrocolloid and silicone types, help maintain a moist healing environment, but repeated removal can disrupt fragile newly formed tissue. Sprayable dressings, on the other hand, provide semipermeable occlusion similar to transparent films, supporting angiogenesis and enhancing dermal structure. In porcine models, these sprayable systems have been shown to promote thicker epidermis and improved vascular density by day 35[103,104].

Antimicrobial Functionality

Self-adhesive bandages primarily function as passive barriers and rarely contain antimicrobial agents. In contrast, sprayable dressings can incorporate active compounds such as silver salts (e.g., AgNO₃), allowing sustained antimicrobial release over 7–14 days with low cytotoxicity and demonstrated effectiveness in both in vitro and in vivo studies.

Stability & Frequency of Changing

Self-adhesive dressings may lose adhesion over time, requiring frequent replacement and potentially causing repeated trauma to the wound site. Sprayable polymer dressings, however, adhere more durably and resist shear forces, reducing the need for frequent changes; porcine studies have reported approximately 25% fewer dressing changes with these systems.

Healing Outcomes & Clinical Evidence

Self-adhesive bandages are effective in promoting wound healing, with silicone dressings providing comparable outcomes while causing less pain than hydrocolloid or foam

alternatives. Sprayable dressings demonstrate similar closure rates in porcine models, along with improved tissue integration and minimal displacement under shear forces[105]

 Comparison between traditional adhesive bandages and sprayable polymer dressings is shown in Table 2.

Table 2: Comparison between traditional adhesive bandages and Sprayable polymer dressing

MARKETED FORMULATIONS:

The marketed formulations of spray bandages are shown in Table 3.

Table 3: Marketed formulations of Spray bandages [78].

 

FILM FORMING MECHANISMS OF SPRAY BANDAGE:

The film-forming drug delivery system applied by spray bandages provides a protective barrier for wounds while permitting breathability without contact. Spray bandages work by providing a protective semipermeable film over the injured surface, whose bond with the skin is therefore close and intimate. The formation of protective film starts when the liquid formulation is applied, consisting of volatile solvents such as ethanol or isopropanol, film-forming polymers, such as polyvinylpyrrolidone, ethyl cellulose, chitosan, plasticizers, and sometimes the active pharmaceutical ingredients, i.e., antibiotics or antiseptics. When this liquid synthesis comes in contact with the skin, the volatile solvents evaporate very rapidly and in doing so this causes the polymers dissolved in them to solidify into a smooth, flexible, and transparent film that adheres firmly to the stratum corneum or the outermost layer of skin. The adhesion mechanism works through strong physical and electrostatic bonding, with the polymer film bonding to skin proteins through hydrogen bonds or Van der Waals forces. The film acts as a bioactive dressing that fulfils several important crucial wound care processes for Critical Parameters Influencing Spray Bandage Performance is shown in Table 4.

Table 4. Critical Parameters Influencing Spray Bandage Performance.

 

Barrier Function: This film will provide an occlusive or semi-occlusive barrier that prevents microbial forms, mechanical trauma, and contamination from the outside environment, as the stratum corneum does.

Retention of Moisture: Spray bandages keep moisture around the wound, which promotes autolytic debridement and keratinocyte migration, which are necessary steps for re-epithelialization and granulation tissue formation.

Allowing Oxygen Exchange: Spray bandage films are in general crafted to allow oxygen exchange; cellular respiration and angiogenesis, thereby laying the baselines for adequate wound healing.

Drug Delivery: If medicate: The active pharmaceutical ingredients, like antimicrobials, if any are incorporated (such as silver sulfadiazine, mupirocin), or just local anaesthetics, get released in a controlled release mechanism through the polymer matrix by diffusion, so that it provides targeted and sustained therapeutic effect at the wound interface.

Adherence to skin and film durability: Good skin adherence without causing trauma on removal is critical. Factors such as film tensile strength, elongation, hydration rate, and skin compliance play a vital role in the effectiveness of this bio adhesive interaction. Adequate elasticity guarantees the bandage conforms to body movements, especially in areas with high mobility like joints.

Benefit of Non-contact Application: The aerosol or pump spray delivery method provides a sterile, touch-free application, which reduces the chance of secondary infection and cross-contamination[106].

There appear to be three film formation mechanisms mentioned in the articles on spray film-forming systems: Crosslinking [Fig. 4], Evaporation-driven [Fig. 5] and Coalescence- driven [Fig. 6]. However, despite the classification of these mechanisms, it is evident that they can be complementary in certain cases, although some mechanisms dominate others. The third coalescence-based mechanism is common in tablet coatings. Typically, a water-based dispersion is prepared, and coalescence happens as the solvent evaporates influenced by surface-mediated forces. Evaporation-based film formation is associated with high solvent content and low solids content. In aerosol spraying, the film formation mechanism likely involves coalescence, whereas in standard spraying, it resembles the evaporation-based process. The nature of the polymers should ideally determine the mechanism and, consequently, the spraying system; however, this has not been well documented in the literature to date, and the techniques currently in use for the creation of spray film- forming systems are more empirical[107].

Figure 4. Crosslinking Film-forming mechanism[107].

Figure 5. Evaporation-driven Film-forming mechanism[107].

Figure 6. Coalescence- driven Film-forming mechanism[107].

DRUG DELIVERY SYSTEMS IN TOPICAL SPRAYS:

The drug present in a topical system penetrates the skin through three primary pathways, which depend on the physicochemical properties of the drug molecule. The main route involves diffusion through keratin-filled corneocytes, while the secondary route occurs via the intercellular spaces between these cells[108]. In certain cases, the drug may also bypass these routes and enter through skin appendages such as hair follicles, sweat glands, or sebaceous glands—this process is referred to as transappendageal transport[109].The epidermis is composed predominantly of keratinocytes (around 95%), along with smaller proportions of melanocytes, Merkel cells, and Langerhans cells. As the body’s largest and most vital organ, it plays key roles in thermal regulation, protection against microbes, and vitamin D synthesis. Its outermost layer, the stratum corneum, serves as the primary structural barrier to drug absorption from topical or transdermal formulations. This layer consists of dead cells rich in proteins and lipids, organized in a “brick-and-mortar” pattern. The spaces between corneocytes are filled with hydrophobic lipids, forming a lipid-enriched matrix arranged into lamellar membranes that envelop each corneocyte [Fig. 7][110].

Figure 7. Drug penetration across skin pathways [110].

For effective transdermal drug delivery system development, drug selection is crucial. Transdermal patches are particularly beneficial for drugs that experience extensive first-pass metabolism, have a narrow therapeutic window, or possess a short half-life requiring frequent dosing, which can lead to poor patient compliance.

Key drug properties and factors to consider for transdermal delivery are shown in Table 5 and Table 6.

Various routes of topical drug delivery of the spray bandages:

Topical drug delivery can be done through 4 different approaches[Fig.8.] which includes—Polymer membrane partition controlled transdermal system, Polymer matrix diffusion controlled system, Drug reservoir gradient controlled system ,Micro reservoir dissolution controlled system.

Membrane Permeation – controlled systems: In this system, the drug reservoir is enclosed within a compartment made of a drug-impermeable laminate and a rate-controlling polymeric membrane (micro-porous or non-porous, e.g., EVA copolymer) with specific permeability. The drug is either dispersed in a solid polymer matrix or suspended in a viscous, non-leachable medium like silicone fluid. A hypoallergenic adhesive layer (e.g., silicone or polyacrylate) ensures close contact with the skin. The drug release rate can be controlled by adjusting the membrane’s composition, thickness, and permeability, providing a steady release. A drawback is the risk of dose dumping if the membrane is accidentally damaged.

 Adhesive Dispersion type system: In this simplified membrane permeation-controlled system, the drug is directly mixed into an adhesive polymer, such as poly(isobutylene) or poly(acrylate), and then applied—via solvent casting or hot melt—onto a flat, drug-impermeable metallic plastic backing to create a thin drug reservoir layer. Over this layer, a non-medicated, rate-controlling adhesive polymer of defined permeability and uniform thickness is added, resulting in an adhesive diffusion-controlled drug delivery system[111-113].

 Matrix Diffusion controlled system: In this method, the drug reservoir is created by evenly dispersing drug particles within a hydrophilic or lipophilic polymer matrix. The medicated polymer is shaped into a disc with a specific surface area and thickness. Drug dispersion can be achieved by mixing finely powdered drug with a liquid or viscous polymer, followed by polymer cross-linking, or by blending the drug with a rubbery polymer at elevated temperatures. Alternatively, the drug and polymer may be dissolved in a common solvent, then moulded and dried by solvent evaporation under heat and/or vacuum. The resulting medicated polymer disc is attached to an occlusive backing, with an adhesive rim applied around its edges for secure placement.

Figure 8. Membrane permeation type system(I), Adhesive dispersion type system(II), Matrix diffusion controlled type system(III), Micro reservoir type of system(IV) [111-113].

MICRO-RESERVOIR TYPE OR MICRO-SEALED DISSOLUTION CONTROLLED SYSTEMS:

This system combines reservoir and matrix diffusion approaches. The drug is first suspended in an aqueous solution of a water-soluble polymer, then dispersed into a lipophilic polymer (e.g., silicone elastomers) using high-energy dispersion, forming microscopic, unleachable drug reservoirs. The dispersion is quickly stabilized by in situ cross-linking of the polymer, creating a medicated disc with fixed surface area and thickness. A biocompatible coating may be added to control release rate. The final transdermal system places the medicated disc at the center with an adhesive rim for skin contact[114-116].

Table 5: Ideal properties for drugs for TDDS [114-116].

Factors Affecting Transdermal Drug Delivery:

1.Patient specific factors:

Skin condition: Healthy, intact skin naturally acts as a barrier, but certain substances such as acids, alkalis, and some solvents can penetrate it. Solvents like methanol and chloroform can extract lipids from the stratum corneum, disrupting its dense structure and creating artificial pathways that allow drug molecules to pass more easily.

 Skin age:Skin permeability is generally slightly higher in younger individuals compared to older adults, though the difference is not dramatic. However, children are more susceptible to toxic effects due to their larger skin surface area relative to body weight. As a result, potent agents like strong steroids, boric acid, and hexachlorophene have been known to cause severe adverse effects in children[117-119].

Table 6: Factors to be considered for transdermal dose calculation [117,118].

 

Physicochemical factors

Hydration of the skin: When skin becomes hydrated, tissues swell, wrinkles soften, and permeability to drug molecules increases.

Temperature and Ph: Penetration rate changes with temperature; cooler temperatures reduce the diffusion coefficient. Adequate clothing helps prevent large fluctuations in skin temperature. Regarding pH, only unionized drug molecules pass easily through lipid membranes. Weak acids and bases dissociate based on the pH and their dissociation values, so the concentration of the unionized form in the applied formulation determines the effective diffusion gradient[120].

Environmental factors

Sunlight: Chronic sun exposure can thin the walls of blood vessels, making skin prone to bruising even with minor injury. Sunlight can also cause pigmentation changes, such as freckles and solar lentigines.

Cold weather: Cold climates often cause skin dryness and itchiness. In response, the skin increases oil production to counteract moisture loss. Regular moisturizers and sufficient water intake can help maintain hydration and skin radiance.

Air pollution: Dust particles can clog pores and promote bacterial growth on the skin, leading to acne or blemishes. In addition, invisible chemical pollutants can disrupt the skin’s protective barrier by breaking down natural oils, reducing moisture retention, and impairing suppleness, all of which can affect drug penetration[121].

BIOLOGICAL PERFORMANCE:

Antimicrobial Efficacy

Prevention of infection is a primary function of spray bandages[122]. A sprayable poly(lactic-co-glycolic acid)/polyethylene glycol nanofiber dressing containing silver nitrate demonstrated significant bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa, while also maintaining a moist wound environment. In a porcine model, this dressing reduced bacterial load and required fewer dressing changes compared to conventional films.

Similarly, a shellac-based liquid bandage containing copper and zinc ions exhibited rapid contact-killing of S. aureus and E. coli in ex vivo assays. The immediate film formation provided a physical barrier against microbial ingress, supporting its use in contaminated wound environments[123].

Biocompatibility:

Spray bandages must be safe for skin and underlying tissues[124]. A water-soluble chitosan spray loaded with human epidermal growth factor -containing liposomes showed no cytotoxic effects in fibroblast cultures. This formulation formed a flexible film on skin, adhered well without irritation, and promoted rapid re-epithelialization in murine excision wounds[125].

Another example, the Gelatin Methacryloyl/Hyaluronic Acid Methacrylate spray containing calcium peroxide for oxygen release, demonstrated excellent cell compatibility and supported fibroblast proliferation in vitro. No adverse reactions were noted in contact assays, suggesting suitability for clinical translation[126].

Wound Healing Acceleration:

Beyond infection control, spray bandages can actively accelerate wound closure[127]. A spray-type alginate hydrogel tested in rat burn models significantly shortened healing time compared to gauze dressings. Histological analysis revealed improved re-epithelialization, collagen deposition, and angiogenesis. Pain scores recorded during dressing changes were lower, indicating a secondary benefit for patient comfort[128].

Oxygen-releasing spray dressings such as Gelatin Methacryloyl/Hyaluronic Acid Methacrylate and Calcium oxide have been shown to enhance cellular proliferation, angiogenesis, and granulation tissue formation in hypoxic wound models. This dual antimicrobial and pro-healing activity is particularly relevant for chronic wounds[129].

Inflammation Modulation and Oxidative Stress Control:

Chronic wounds often exhibit prolonged inflammation and oxidative stress, which can delay healing[130]. Some sprayable hydrogels incorporate reactive oxygen species scavengers or bioactive ions to reduce oxidative damage[131]. For example, zinc-modified metformin-loaded thermoresponsive hydrogel sprays reduced inflammatory cytokines while promoting angiogenesis in rodent wounds. Such approaches aim not only for closure but also for better quality of regenerated tissue[132].

Patient Comfort and Ease of Use:

Patient comfort and ease of application are important practical metrics. The poly(lactic-co-glycolic acid)/polyethylene glycol spray reduced dressing-change frequency due to sustained antimicrobial action and moisture retention. The alginate spray’s ability to reduce procedural pain during dressing changes highlights its potential for burn patients or those with fragile skin. Spray systems also eliminate the need for adhesive tapes, reducing skin trauma upon removal[133].

EVALUATION PARAMETERS OF FILM FORMING SYSTEMS:

Film  formation:

Film-formation is evaluated and rated as complete and uniform, incomplete or non-uniform, with or without precipitation of the film-forming polymer. The cosmetic aspects of the film are given in terms of transparency or opaque, sticky or dry, peelable or non-peelable[134].

Film flexibility:

Film flexibility is evaluated on the basis of cracking and skin fixation and this is determined by stretching the skin in 2–3 directions. The film is rated flexible if there is no cracking or skin fixation and non-flexible if there is cracking and skin fixation.

Drying time:

For the evaluation of the drying time the formulation is applied to the inner sides of the forearm of a volunteer. After a fixed time period a glass slide is placed on the film without pres- sure. If no liquid is visible on the glass slide after removal, the film is considered dry. If remains of the liquid are visible on the glass slide the experiment is repeated with an increase in drying time. A good film-forming system should have a minimum drying time to avoid long waiting time for the patient[135].

Stickiness:

The stickiness of the film formed is determined by pressing cotton wool on the dry film with low pressure. Depending on the quantity of cotton fibres that are retained by the film, the stickiness is rated high if there is dense accumulation of fibers on the film, medium if there is a thin fiber layer on the film and low if there is an occasional or no adherence of fibers. This evaluation parameter is essential, as the formulation should be non-sticky to avoid adherence to the patients’ clothes[136].

Mechanical properties:

The polymeric films are produced by solvent evaporation on a Teflon plate, the mechanical properties of the films are determined with a tensile tester, tensile strength (σ) is calculated as:

σ = Fmax A(Nm2)

where, Fmax (N) is the maximum force and A (m2) is the cross- sectional area[137].

 

 

 Determination of the water vapor permeability:

The water vapor permeability is defined as the quantity of water transmitted through a unit area of film in unit time.

These water vapor permeation data are important in determining the permeation characteristics of the film as they have influence on skin properties like hydration of stratum corneum, blood flow, and skin temperature[138].

 Swab studies:

A swab test can be performed to evaluate the residence time of the film forming system. For adhesion testing, glass was used as a polar, hydrophilic substrate. Glass was chosen as a test surface because films adhering strongly to it would also show strong adherence to skin because both materials display a polar surface structure[139].

Film topography:

Atomic force microscopy is used to analyze the topography and mechanical properties of polymeric films, enabling comparison of the films’ mechanical behavior with that of skin. It produces nanoscale images that reveal the films’ homogeneity and surface roughness, without requiring any special sample preparation beforehand.

 Film homogeneity:

Raman spectroscopy provides information about the chemi- cal composition of the polymeric films. The chemical maps obtained from Raman spectra provide a measure of chemical homogeneity of films. Techniques based on Raman scattering can also be used to track the permeation of topically applied compounds through the skin[140].

 In vitro diffusion study:

In vitro diffusion studies are conducted to predict the drug’s permeation behavior in vivo. For this, a Franz diffusion cell is commonly employed to evaluate the release profile of the drug from the film-forming system. The apparatus consists of two compartments, the donor and the receptor separated by a diffusion membrane (such as egg membrane or cellophane). The donor compartment remains open to the atmosphere, while the receptor compartment holds the diffusion medium and is equipped with a sampling arm for collection. A measured amount of the drug-loaded film-forming formulation is placed in the donor compartment, and samples withdrawn from the receptor medium are analyzed using an appropriate spectroscopic technique to assess drug release.

 Ex vivo permeation studies:

Ex vivo permeation studies are carried out to evaluate the influence of the skin barrier on the film-forming system. These studies typically employ a Franz diffusion cell or Keshar Chien diffusion cell, with rat skin mounted between the donor and receptor compartment placing the stratum corneum towards the donor side and the dermis towards the receptor side. The formulation is applied onto the skin surface, where it forms a film upon drying. The receptor compartment is filled with phosphate-buffered saline (pH 7.4) maintained at 37 ± 0.5 °C. Samples are withdrawn at predetermined intervals and analyzed using an appropriate spectroscopic technique[141].

Skin penetration studies:

In skin penetration studies, the formulation is uniformly applied to the skin using a pipette or spatula. At predetermined time intervals (e.g., 15 min, 1 h, 3 h, 6 h, 8 h, etc.) after application, the residual formulation is removed. The film is then wiped off with cotton pads, and the drug content on the pads is measured, representing the amount of drug left in the film. The quantity of drug that has penetrated the skin is determined by subtracting this residual amount from the total drug initially present in the formulation[142].

CHALLENGES:

Spray film-forming systems have attracted increasing attention as topical and wound-care delivery platforms due to their ability to form in situ protective films that prolong drug residence time, reduce cross-contamination, and potentially accelerate wound healing. Despite these advantages, the development and regulatory translation of spray film-forming systems remain challenging. A recurring limitation identified across the literature is the fragmented nature of available data and the lack of standardized characterization methodologies. Inconsistencies in the evaluation of sprayability, drying time, mechanical properties, occlusivity, and biocompatibility hinder comparison between studies and complicate regulatory classification as either drug or medical device, thereby slowing product registration and clinical adoption.

Compared with conventional topical dosage forms such as creams, ointments, semisolids, and patches, spray-based film-forming systems offer several practical advantages, including non-contact application, improved sterility, uniform drug distribution, and flexible dosing. These attributes are particularly relevant in wound management, where minimizing contamination and improving patient compliance are critical. In contrast, traditional topical formulations have been associated with hypersensitivity reactions, blistering, poor adherence to irregular skin surfaces, and cross-contamination arising from finger application. However, spray film-forming systems also present notable limitations, including formulation instability during solvent evaporation, drug recrystallization, scale-up challenges, and variability in in-use performance, all of which must be addressed during development.

The performance of spray film-forming systems is governed by a complex interplay of formulation and device-related parameters. Polymer type and concentration, solvent system, plasticizer selection, excipients, and spray device characteristics collectively influence critical quality attributes such as spray pattern, droplet size, film morphology, flexibility, drying time, viscosity, pH, and bioadhesive strength. Both natural and synthetic polymers with in situ film-forming capability have been explored; however, optimizing polymer composition while maintaining mechanical integrity, drug stability, and patient comfort remains a key challenge. The absence of harmonized evaluation protocols further limits rational formulation optimization and cross-study comparability[143].

In the context of wound care, additional considerations such as moisture vapor transmission rate, occlusivity, cytocompatibility, and irritation potential become particularly important. While increased occlusion may enhance drug retention and barrier function, excessive occlusivity can promote maceration and delay healing. Moreover, mechanically robust film-forming chemistries, such as nitrocellulose-based systems, often rely on organic solvents or high polymer loads, which may increase irritation risk and limit their suitability for compromised skin. These tradeoffs underscore the need for systematic assessment of mechanical durability versus biocompatibility, as well as manufacturing strategies that minimize residual solvent content.

Controlled-release spray film-forming systems further expand the formulation design space. Approaches such as polymer blending, plasticizer modulation, and incorporation of nanoparticle carriers have been employed to modulate drug release profiles. However, these strategies frequently influence film formation kinetics, mechanical properties, and surface morphology, complicating formulation optimization. Achieving predictable and reproducible drug release while maintaining thin, flexible, and conformable films capable of withstanding movement and shear at wound sites remains challenging. Additionally, conventional in vitro release and permeation models often fail to adequately predict in-use behavior, highlighting the need for standardized test systems that better simulate wound environments, exudate, and mechanical stress[144].

Operational and manufacturing challenges are also widely reported in the literature. Reproducible spray performance parameters, including dose per actuation, droplet size distribution, spray cone angle, and solvent evaporation profiles, are frequently under-reported despite their importance to product performance[145]. Packaging compatibility, particularly interactions between formulation components and container–closure systems, further affects product stability and reliability. Stability concerns such as drug precipitation, phase separation, and transfer of the formed film to clothing or surrounding surfaces may compromise consistent dosing and patient acceptability. Consequently, several authors advocate for the adoption of standardized bench-top and in-use performance tests, including spray characterization, adhesion and removal force,moisture vapor transmission rate, and cytotoxicity assessments using damaged skin models[146].

From a clinical perspective, evidence supporting the use of spray film-forming products is strongest for minor cuts and abrasions, whereas data for chronic and complex wounds, such as diabetic foot ulcers and pressure injuries, remain limited and heterogeneous. Clinical outcomes including time to wound closure, infection rates, pain on application, and patient-reported acceptability are inconsistently defined and reported across studies. As a result, recent reviews emphasize the need for well-designed clinical trials with standardized endpoints to clarify the therapeutic role of spray film-forming systems relative to conventional wound dressings. Overall, while spray film-forming systems represent a versatile and attractive approach for topical and wound drug delivery, coordinated advances in formulation science, standardized evaluation methodologies, manufacturing practices, and clinical evidence are required to fully realize their clinical and regulatory potential[147].

 

RECENT ADVANCES:

New film-forming systems and matrices: Adaptive, oxygen-permeable polymers (such as silicones, cellulose derivatives and acrylates) are used in modern spray film-forming systems to produce breathable, quick-drying barriers that maintain drug contact on skin. Their composition, mechanics, and benefits over conventional dressings are detailed in thorough reviews conducted in 2022–2023. Using Box-Behnken designs, 2023–2024 work optimizes non-pressurized (pump) liquid bandages as propellant-free alternatives by adjusting drug release, adhesiveness, drying time, and film integrity[147]. To address the previous deficiency of standardized test methods, methodological papers suggest standardized screening parameters (such as viscosity ranges, spray angle, drying time, tack/adhesion)[148].

Built-in antimicrobial/antifouling functionality: By incorporating antiseptics and antimicrobial metals to sprayable films, infection control is enhanced without the need for frequent dressing changes. Zinc/Copper-modified shellac liquid bandages produced quick, long-lasting films with strong barrier qualities and antibacterial activity, according to a 2020 study.  Silver sulfadiazine is also incorporated into film-forming sprays by recent formulations, which show adjustable mechanical characteristics and on-skin performance.

Hemostatic and bioadhesive sprayables for acute bleeding: Studies from 2024–2025 show that sprayable/broadcastable hemostats, such as oxidized cellulose nanofiber hydrogels and bioadhesive polyphenol powders, can quickly seal wet, irregular wounds and reduce hemostasis times in preclinical models. These are administered by spraying and deal with non-compressible bleeding, which is a significant area for spray bandages, even though they are not always "films" [149].

Stimuli-responsive and “smart” functions: Reactive oxygen species scavenging and antimicrobial action are increasingly integrated into sprayable hydrogels and films, which speed up closure while regulating the wound microenvironment .Although many of the devices are patches, the same materials strategies (conductive fillers, responsive polymers) are being adapted to sprayable matrices for conformal coverage. The broader "smart dressing" trends—sensing pH, temperature, moisture, or releasing drugs on-demand—are developing quickly.

Toward dermatologic and clinical use cases: In addition to minor cuts, film-forming sprays are now being used as an adjuvant treatment for dermatological conditions like psoriasis and eczema, with clinical evaluations of patient acceptability and safety/tolerability. These studies support wear time, skin feel, and flexibility—all important factors for practical adoption.

Practical formulation trends: While polymer/excipient selection strikes a balance between elasticity, adhesion to wet tissue, and painless removal, solvent systems are being optimized for quick evaporation, minimal irritation, and propellant-free delivery. Excipient selections and performance trade-offs between sprays and gels/patches are compiled in recent reviews[150].

CONCLUSION

Spray film-forming systems represent a significant advancement in topical and transdermal delivery, offering rapid, non-contact application and enhanced patient comfort compared to traditional dressings. Their polymer-based matrices enable prolonged drug retention, reduced contamination risk, and accelerated wound healing while maintaining an optimal moist microenvironment. Despite these advantages, spray film-forming systems still face critical challenges, including formulation instability, solvent-related irritation, and the lack of standardized evaluation protocols for sprayability, mechanical integrity, and occlusivity.

Recent studies highlight notable progress in adaptive, oxygen-permeable polymer systems and propellant-free designs that improve drying time, flexibility, and film integrity while minimizing irritation. Additionally, incorporation of antimicrobial metals and bioadhesive polymers enhances infection control and barrier performance, aligning with current trends toward multifunctional and stimuli-responsive “smart” spray dressings . Emerging hemostatic and bioadhesive sprayables also demonstrate potential in managing acute bleeding and irregular wound surfaces, expanding clinical applicability beyond minor cuts.

However, widespread adoption remains hindered by fragmented data, regulatory ambiguity, and inconsistent clinical endpoints in chronic and complex wounds. Addressing these gaps through harmonized testing frameworks and better-designed clinical trials will be essential for ensuring reproducibility, scalability, and regulatory clarity.

Overall, spray bandages bridge pharmaceutical innovation and clinical practicality, offering a promising route toward patient-tailored, on-demand wound management systems. With continued development in polymer chemistry, smart functionalities, and standardized evaluation methods, spray film-forming systems are poised to become a transformative tool in modern wound care..

CONFLICT OF INTEREST

We the authors of the manuscript titled "From Mist to Medicine: Wound Healing Revolution with Liquid Sprays" present our work as a requirement for the Pharmacy program. The work is based solely on a review of existing scientific literature and has been conducted independently. The authors of the manuscript declare that no financial relationships or commercial connections or professional ties or personal associations exist which might create a conflict of interest.

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