A Comphrensive Review on Nano Sponge as Drug Delivery System

Aman Shaikh*, Dr. GJ khan, Imran Kalam,Shaikh Md. Moiz, M Sohil M Shabbir

JIIU’s Ali Allana College of Pharmacy Akkalkuwa, Dist-Nandurbar -425415, Maharashtra, India

*Correspondence: shaikhaman3702@gmail.com; (Tel: +91 9075114386)

INTRODUCTION:

Drug delivery is the process of creating formulations that convey medicinal compounds into the body and enable them to produce the intended therapeutic effects. Medical researchers have long struggled with medication delivery and targeting, ensuring that the administered medicine reaches the intended location and controlling the release of the drug to prevent overdose.(1) The necessary quantity of medication must be delivered to the site of action in order to achieve the intended therapeutic response, and the rate of drug release must be subsequently controlled. Drug distribution outside the target tissues appears wasteful and unnatural, which is the primary cause of toxicity. Transporting a medication to receptors, organs, or other areas of the body that the user wishes to administer the medication to is known as focused drug delivery (2) Drug compounds that are poorly soluble in water can become more soluble thanks to nano sponges' capacity to transport both hydrophilic and lipophilic molecules. This technology is regarded as a unique strategy that provides a topical medication delivery system that is controlled. It effectively provides components with fewer adverse effects, better stability, more elegance, and more formulation flexibility.(3) Nanoparticles come in a wide variety of forms, such as dendrimers, carbon nanotubes, micellar systems, solid-lipid nanoparticles, polymeric nanoparticles, nano emulsions, and nano sponges. It is easy to transport the chemical for parenteral delivery in saline, sterile water, or other aqueous solutions (4)  Medical experts have long struggled to target medication delivery, or how to send the medicine to the proper area in the body and regulate its release to avoid overdosing. This issue could be resolved by the creation of new, intricate molecules known as nano sponges. (5) The manner of administering desired pharmaceuticals has been the focus of such efforts for a considerable amount of time. In the twenty-first century, nano sponges can be injected or given orally, much like other contemporary medications. Well-known nano sponges include those made of hyper-cross-linked polystyrene, silicon nanoparticles, titanium nanoparticles, and cyclodextrin. Nano sponges are a new type of hyper-cross-linked polymer based colloidal structure consisting of solid nanoparticles with colloidal and nano sized cavities.(6) A novel form of colloidal structure based on hyper-crosslinked polymers, Nano sponges are composed of solid nanoparticles with colloidal and nano-sized cavities. Examples of well-known Nano sponges are those composed of cyclodextrin, silicon nanoparticles, titanium nanoparticles, and hyper-crosslinked polystyrene.   

Figure 1: Nano sponges with a cavity for drug loading, structurally

Figure 2: Formation of Nano sponges.

Nano sponges with the required size and drug release over time may be produced by varying the cross linker to polymer ratio. The relatively simple chemistry of the polyesters and cross-linking peptides in nano sponge adds to its engineering potential, in contrast to many other nanoscale drug delivery methods. These nano sponges can become magnetized when they are created in the presence of materials that have magnetic properties. Nano sponges can enter the veins and lungs because to their minute shape. (7)

Ø  Types of Nano sponges. (2)

Ø  EXCIPIENTS USED IN NANO SPONGE:

Ø   

DRUGS USED IN NANO SPONGE DELIVERY(6)

Ø   

Ø  ADVANTAGES OF NANO SPONGE: 

·         By permitting the trapping of the same, it lessens the adverse effects of various components.

·         It can aid in masking the drug's disagreeable taste.

·         The formulation's stability can be improved. 

·         It is possible to produce extended release action for up to 12 hours.

·         The substance utilized in this technique can act as a barrier to prevent the medicine from being destroyed too soon within the body.

·         Because of their average pore size of 0.25μm, which prevents germs from penetrating, they are self-sterilizing.

·         They are more elegant, more stable, and offer better formulation flexibility.(4)

Ø  Disadvantages of Nano sponges:

·         Because of their tiny particle size, which limits medication loading, dosage dumping can occasionally happen.

·         Only tiny molecules can be trapped by a Nano sponge.

·         The capacity of Nano sponges to encapsulate tiny molecules makes them unsuitable for big molecules.

·         The degree of crosslinking has an impact on drug loading capacity as well; crosslinking calculates the amount of empty space that is accessible in Nano Sponge for drug loading. Because of the cross linker's early breakdown, there is a risk of dosage dumping.

·         Here are a few benefits and drawbacks of using Nano Sponge in a unique medication delivery system (2).

Ø  Composition and of Nano sponges:

  Nanoparticles are complex structures composed of long, linear molecules that are folded by cross-linkers into a spherical form around the size of a protein. Here is a list of the five main parts of Nano sponges. 

A. Polymer

B. Cross linking agent 

C. Surfactant 

D. Drug substance 

E. Solvent

A.    Polymer:

The speed at which nano sponges develop and discharge material can be influenced by the type of polymer utilized. The polymers are used to encapsulate the active pharmacological component or to interact with the medicinal substance. A drug molecule of a particular size for complexation should be able to enter the nano sponge's cavity due to its size. The ability of the polymer to crosslink is impacted by the replacement of functional and active groups. To get medications to the appropriate places at the right times, the polymer must be able to bind to the proper ligands. Eudragit, ethyl cellulose, and polymethyl methacrylate are a few examples.In Nano Sponge drug delivery systems, cyclodextrins and its derivatives are also employed as polymers. 

B.     Crosslinking Agent:

The choice of crosslinking agent is influenced by the chemical composition of the polymer as well as the medication of choice. Dichloromethane is the most often used cross linker for topical therapies. Drug entrapment in the polymers and particle size increased as internal phase volume increased without any apparent pattern because of the reduction in internal phase viscosity. Using 20 milliliters of dichloromethane, the nano sponges with the highest trapping effectiveness were produced. Methanol, ethanol, and dichloromethane are a few examples.

C.    Drug Substance:

The following qualities are necessary for drug molecules to be created as nano sponges:

• The range of molecular weight is 100–400 Daltons.

• There should be no more than five condensed rings in a drug molecule.

• Water solubility of molecules should be less than 10 mg/ml.

• The active moiety's melting point need to be lower than 250°C.

D.    Surfactants:

A common surfactant used in the production of nano sponges, polyvinyl alcohol is crucial to the development of nano sponges with reduced particle sizes. It was found that when the concentration of surfactant increased, so did the particle size. Aggregates are produced as a result of foaming brought on by higher surfactant concentrations.

Ø  METHOD OF PREPARATION OF NANO SPONGE:

1.      MELT METHOD:

Mix the cyclodextrin polymer with cross-linkers such glutaraldehyde, diisocyanate, diphenylcarbonate, and carboxylic acid anhydrides, then melt the mixture.

After gently mixing all the components, they are placed in a 250 ml flask and heated to 1000 c. For five hours, the reaction is carried out. beneath a magnetic stirrer. After allowing the mixture to cool, the result is broken down.

In order to remove unreacted excipients and byproducts, the obtained result is cleaned using preferred solvents.

    2. MICROWAVE ASSISTED SYNTHESIS:

One of the most significant benefits of using microwave-assisted synthesis, a straightforward technique for creating cyclodextrin-based Nanoparticles, over alternative approaches is its fourfold reduction in reaction time, high crystallinity, and uniform particle size distribution.M. (10)

3.      SOLVENT METHOD:

A preferred solvent, such dimethylformamide, was mixed with the polymer.

This combination was combined with an additional quantity of cross linker. The reaction was accomplished at temperatures ranging from 10°C to the solvent's reflux temperature over a period of 1 to 48 hours. Following the completion of the reaction, the solution was allowed to cool to room temperature. The product was then added to a large volume of distilled water, filtered under vacuum, and finally purified by continuing the Soxhlet extraction process with ethanol. To create a uniform powder, the end product was vacuum-dried and then ground in a mechanical mill.

4.      LOADING OF DRUG INTO NANO SPONGE:

To prevent aggregates, stop the nano sponges in water and sonicate them. Then, centrifuge the suspension to extract the colloidal pieces. After separating the supernatant, freeze-dry the sample. Aqueous nano sponges are later added to a solution.It is given extra doses of the medication. This is then continuously stirred for a certain amount of time to allow for complexation.Centrifugation is used to separate the uncomplexed medication after complexation. Finally, Solvent evaporation is used to get the solid crystals of nano sponges (11). 

CHARACTERIZATION OF NANO SPONGES:

The following is a list of the characterization techniques for the drug/nano sponge complex.

Ø  Solubility studies:

Phase solubility diagrams show the degree of complexation. The phase    solubility method, which Higuchi and Connors describe, is the most popular method for studying inclusion complexation. The drug was added to an Erlenmeyer flask that contained an aqueous solution of different percentages of Nano sponges. The flask was shaken on a mechanical shaker at room temperature, and when a steady state was reached, the suspension was filtered by centrifugation. High performance liquid chromatography was used to analyze the solution to determine the drug concentration (9).

Ø  Microscopic study

Drugs and Nano sponges may be studied at the tiny level using scanning and transmission electron microscopes. The formation of an inclusion complex is shown by the difference between the crystallization state and the finished product that can be seen under an electron microscope.

Ø  Zeta potential determination

The difference in potential between the immobile layer and the dispersion medium, two fluid layers trapped with dispersed particles, is known as the zeta potential. Zeta potential is the main measure of the colloidal dispersion's stability. A zeta seizer or an extra electrode added to particle size analysis equipment can be used to measure the zeta potential. A colloidal dispersion's zeta potential value increases with its stability.

Ø  Thermodynamical method

It is possible to determine if drug molecules or particle changes occur before to the heat degradation of  Nano sponges using the thermo-chemical method. Drug particles can change by a variety of processes, including melting, evaporation, oxidation, disintegration, and polymeric changes. The changes in the drug molecules indicate the formation of a strong compound. 

Ø  Particle size and polydispersity

The dynamic light scattering approach is utilized to determine the particle size using the 90Plus particle size determination application. Dynamic light scattering (DLS) is defined as a technique for figuring out the size distribution profile of nanoparticles. Lastly, the particle diameter and polydispersity index (PDI) may be computed.

Ø  Thin layer chromatography (TLC)

One way to describe TLC is as an evaporative or non-volatile mixture separation technique. It can be helpful in determining if a complex between the drug and the nano sponges is developing if the Rf value of a particular drug molecule is within the permitted range in this method.(7)

Ø  Factors affecting Nano sponge formulation

Type of polymers and Crosslinking agents 

The kind of polymers utilized determines how the nano sponges are made and how well they work. The cavity size that the polymeric material provides is crucial for improved drug molecule complexation in the formulation.

Compared to α and γ cyclodextrins, hydroxy propyl β-cyclodextrin has a higher propensity for forming complexes with medicinal molecules. The transformation of molecular nanocavities into three-dimensional nonporous structures is the result of the crosslinking agents. Nano sponges can be water soluble or insoluble, depending on the type of crosslinking agent used.  Epichlorohydrin, for instance, is employed as a crosslinking agent in the creation of hydrophilic Nano Sponge. Drug absorption across biological membranes is improved and the rate of drug release is altered using hydrophilic nano sponges. Hydrophobic compounds are made from diphenyl carbonate and carbonyl diimidazole. Using nano sponges as a vehicle for long-term medication release.

Ø  Nature and type of drug molecule

The choice of polymers and copolymers in the formulation is based on the kind and characteristics of the therapeutic molecules. Important considerations in the formulation include the therapeutic substance's hydrophilic and lipophilic properties as well as the active molecule's dosage. Using medications with a high melting point does not result in a stable complex. 

Ø  Temperature

Temperature has a significant impact on drug polymer complexation. The stability of drug polymer complexes often decreases as the temperature rises, possibly as a result of a decrease in the drug-nano sponge interaction. 

Ø  Degree of substitution

The ability of the nano sponge complex to form depends on the position, kind, and quantity of substituents on the parent polymeric molecule. The quantity of substituents present directly correlates with the degree of cross linking. Higher levels of cross linking are necessary to create nano sponges with very porous mesh types. (14) 

APPLICATIONS OF NANO SPONGES

1 In anticancer therapy:

Anticancer medications can be delivered via Nano Sponge technology. This approach reduces tumor development more effectively than a dry medication injection.

2 Antiviral application:

Nano sponges are administered via the pulmonary and nasal routes. It targets viruses like influenza and rhinovirus that can cause RTIs by delivering antiviral drugs via RNA to the lungs or nasal pathway via a nano carrier. The drugs zidovudine, saquinavir, and acyclovir are employed as nano carriers. 

3 Nano sponges in stability enhancement:

 Iitraconazole is a BCS Class-II medication with low bioavailability and strong penetration. Drug solubility is increased by a factor of 27 thanks to the nano sponges. When copolyvidonum is used as a supportive ingredient in the creation of Nano Sponge, These were more than 55 times. Reaction between copolyvidonum and the hydrophobic group of Iitraconazole, and enhances the medication's wetting ability or lowers the crystallinity of medication

4 Nano sponges in drug delivery:

These can be made in a variety of dose forms, including topical, aerosol, parenteral, capsules, and tablets. An antifungal medication called econazole nitrate is used topically to reduce the symptoms of dermatophytosis, superficial candidiasis, and skin infection, offered as a lotion, ointment, cream, or solution. Econazole is administered to the skin, and for treatment to be successful, a high level of concentration is needed. These are composed of these Nano Sponge-loaded emulsion solvent diffusion methods. in hydrogel, which serves as a local depot for long-term medication release.

5 Nano sponges as a carrier for delivery of gases

A variety of gases are used in medicine for both diagnostic and therapeutic purposes. Hypoxia, which is brought on by an oxygen shortage, is linked to a number of illnesses, including cancer and inflammation. These can occasionally be challenging to provide doses and oxygen in a therapeutic setting. The formulation of Nano Sponge can be such is an oxygen delivery system that may be applied topically and has the capacity to to gradually store and release oxygen over time.

6 Nano sponges in enzyme immobilization:

Lipases are especially affected by enzyme immobilizations, which improve their stability and alter characteristics like enantio selectivity and reaction speeds. High catalytic performances for pseudomonas fluorescents have been observed. lipase adsorbed on a novel kind of Nano Sponge based on cyclodextrin.

7 Nano sponge for oral drug delivery:

The holes of nano sponges speed up the solubilization of poorly soluble medications by allowing the drug to enter the pores. The formation of nanoparticles increases the surface area and speeds up solubilization.  (15) 

8   Purification of water:

Beta-cyclodextrin Nano Sponge is entirely insoluble in water and has the ability to encapsulate organic contaminants from water, making it suitable for removing organic pollutants from water. Porous ceramic filters can be.These Nano Sponge particles are infused to create organic-inorganic hybrid filters.module. It has been demonstrated that these hybrid filter modules efficiently clean water.and employ a range of water contaminants. (12)

CONCLUSION:

The original purpose of the nano sponge was to apply the medications topically. Since they may be utilized to solubilize poorly water soluble medicines and provide delayed release, these colloidal carriers have recently been developed and proposed for drug delivery increase a drug's bioavailability and, in some situations, alter its pharmacokinetics attributes.Using the cutting-edge technique of encasing medication in polymeric materials improved formulation, controlled site-specific medication release, and Nano Sponge technology It enables pharmaceutical dosage, stability, effectiveness, and patient compliance. By varying the cross-linker to polymer, one may modify the particle size and release rate. proportion as well as the stirring speed. Various dose forms, such as aerosol, parenteral. Nano sponges can be used to make topical, pill, and capsule formulations. Potential uses include catalysis, biomedicine, agrochemistry, cosmetics, and bioremediation processes in addition to the drug delivery sector. Clinical trials can determine the effectiveness and safety of medications administered using Nano Sponge, the Pharmaceutical firms will benefit greatly. Therefore, nano sponges are beneficial for medication delivery systems that are site-specific and targeted. (13)

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