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.
Method:
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 counter plots 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 highest entrapment efficiency. Resulting nanoparticles revealed spherical
morphology with 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 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.