Abstract

Objective: The aim of the present study was to design a surface modified chitosan nanoparticle system for vaginal delivery of acyclovir for effective drug uptake into vaginal mucosa.

Methods: Acyclovir-loaded chitosan nanoparticles, with and without modification by poloxamer 407, were prepared by ionic gelation method. The effects of two independent variables, chitosan to sodium tripolyphosphate mass ratio (X1) and acyclovir concentration (X2), on drug entrapment in nanoparticles were studied using 32 full factorial design. The surface response and counterplots were drawn to facilitate an understanding of the contribution of the variables and their interaction. The nanoparticles were evaluated for drug entrapment, size with zeta potential, morphological analysis by TEM, solid-state characterization by FTIR, DSC, XRD, in vitro dissolution, in vitro cell uptake using HeLa cell line and in vivo vaginal irritation test in Wistar rats.

Results: Chitosan nanoparticle formulation with chitosan to sodium tripolyphosphate mass ratio of 2:1 and acyclovir concentration of 2 mg/mL resulted in the highest entrapment efficiency. The resulting nanoparticles revealed spherical morphology with a particle size of 191.2 nm. The surface modification of nanoparticles with poloxamer resulted in higher drug entrapment (74.3±1.5%), higher particle size (391.1 nm) as a result of dense surface coating, lower zeta potential and sustained drug release compared to unmodified nanoparticles. The change in the crystallinity of the drug during nanoparticle formulation was observed in DSC and XRD study. Cellular uptake of poloxamer-modified chitosan nanoparticles was found to be higher than chitosan nanoparticles in HeLa cells. Safety of nanoparticle formulations by vaginal route was evident when tested in female rats.

Conclusion: Conclusively, poloxamer-modified CH NP could serve as a promising and safe delivery system with enhanced cellular drug uptake.

Keywords: Chitosan nanoparticles, poloxamer, mucus penetrating nanoparticles, vaginal delivery, acyclovir, genital herpes.

Graphical Abstract