Fabrication of acyclovir-loaded flexible membrane vesicles (FMVs): evidence of preclinical efficacy of antiviral activity in murine model of cutaneous HSV-1 infection

Drug Deliv Transl Res. 2017 Oct;7(5):683-694. doi: 10.1007/s13346-017-0417-0.

Abstract

The present investigation focuses on the development and evaluation of acyclovir-loaded flexible membrane vesicles (ACY-FMVs) and evaluates their targeting potential to localize the drug into skin layers. The drug-loaded FMVs were prepared by thin-film hydration method and characterized for various attributes including micromeritics, entrapment efficiency, vesicle shape, size, and degree of deformability. The values of particle size and zeta potential of the developed carrier system were found to be 453.7 nm and - 11.62 mV, respectively. The system was further incorporated into a hydrogel and evaluated for skin permeability and retention characteristics in comparison to marketed formulation. The developed formulation demonstrated enhanced retention of drug deep inside the skin layers which can probably decrease the frequency of application of the drug, thereby reducing its adverse effects. Skin irritancy studies performed on Laca mice skin proved the safety and non-irritant nature of ACY-FMVs. The pharmacodynamic studies on murine model for HSV-1 infection demonstrated immense potential and safety of topically applied ACY-FMVs. However, more intensive studies need to be pursued to explore and exploit the potential of lipid-based systems in anti-viral therapeutics. These preclinical findings provide a hope for corroborating the efficacy in clinical situations.

Keywords: Acyclovir; Flexible membrane vesicles (FMVs); Retention; Skin permeation; Topical delivery.

MeSH terms

  • Acyclovir / administration & dosage*
  • Acyclovir / chemistry
  • Acyclovir / pharmacokinetics
  • Administration, Topical
  • Animals
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics
  • Chemistry, Pharmaceutical
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Drug Carriers
  • Herpes Simplex / drug therapy*
  • Liposomes
  • Mice
  • Particle Size
  • Skin Absorption
  • Vero Cells

Substances

  • Antiviral Agents
  • Drug Carriers
  • Liposomes
  • Acyclovir