Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

ABSTRACT: We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70?nm size, with encapsulation efficiency of 63?±?1.9% of Cur &61.5%?±?1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59?±?1.34%; EFV: 58.4?±?1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV?+?Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-? in vaginal tissue and plasma compared to soluble EFV?+?Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV?+?Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV?+?Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

SUBMITTER: Lakshmi YS 

PROVIDER: S-EPMC4858693 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature