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