A Mucoadhesive In situ Gel of Valaciclovir Xanthan Gum Nanoparticles for Genital Herpes Management.

BACKGROUND

Valaciclovir, a prodrug of acyclovir, is used to treat herpes simplex virus infections. The pharmacokinetics of the drug, namely, low oral bioavailability and short half-life, demands an alternative drug delivery system. Since the drug normally targets virus-infected cells and is metabolized into active acyclovir, its therapeutic effect can be achieved through both local and systemic action when administered vaginally. The innate physiological characteristics of the vagina limit long-term drug availability in the vaginal region.

OBJECTIVE

This study aimed to propose a nanoparticle-loaded in situ gel as a drug delivery system to achieve both local and systemic effects of the drug.

METHODS

Ionotropic gelation-high-speed homogenization was adopted to prepare xanthan gum nanoparticles, where crosslinking agents consisted of a combination of sodium citrate and aluminium chloride. Design Expert Software V13 was used to screen the formulation and processing variables. The nanoparticles were characterized by particle size, zeta potential, morphology, drug loading, and in vitro drug release. The selected nanoparticles were combined with 20% w/v poloxamer 407 and 2% w/v HPMC to produce an in situ mucoadhesive gel, and ex vivo drug permeation was established.

RESULTS

Drug loading ranged from 79.92±0.11 to 95.52±0.11%. During the 12-hour investigation, drug release was promising. The optimum formula exhibited a zeta potential of -18.6 mV and an average particle size of 117.0 nm. The optimized nanoparticle permeability coefficient was fourfold higher than that of the drug-embedded gel. The in situ gel's adhesion strength (0.784 N) revealed adequate mucoadhesive properties.

CONCLUSION

Nanoparticulate mucoadhesive gels are a promising approach for the management of genital herpes infection.