ABSTRACT:
Herpes labialis, commonly referred to as cold sores, is a highly prevalent recurrent orofacial infection caused primarily by Herpes Simplex Virus type 1 (HSV-1). Although conventional antiviral agents such as acyclovir and penciclovir are clinically effective, their therapeutic outcomes are significantly limited by poor aqueous solubility, inadequate skin penetration, and subtherapeutic local concentrations at the site of infection. Microemulsions (MEs), defined as thermodynamically stable, optically isotropic, and nanoscale dispersions of immiscible liquids stabilized by surfactant cosurfactant systems, have emerged as highly promising platforms for enhancing antiviral drug delivery to perioral and labial tissues. This review provides a comprehensive overview of microemulsions with respect to their definition, historical background, composition, classification, Winsor phase behavior, and physicochemical characteristics. The formulation strategies relevant to herpes labialis including topical, transdermal, and buccal routes are critically evaluated. The pathophysiology of herpes labialis, including viral replication, immune evasion, and latency mechanisms, is discussed in the context of targeted therapy. Special emphasis is placed on the ability of microemulsion-based systems to enhance drug solubility, permeation across the stratum corneum, local bioavailability, and sustained drug release. The advantages and challenges of microemulsion-based antiviral drug delivery systems are systematically assessed, and future prospects including nanostructured lipid carriers, self-microemulsifying drug delivery systems (SMEDDS), and biopolymer-reinforced microemulsion gels are highlighted. Overall, this review underscores the transformative potential of microemulsions as advanced, patient-compliant, and efficacious carriers for the management of herpes labialis.