title: 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-α 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.
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
authors.forename: Yeruva Samrajya
authors.initials: YS
authors.lastname: Lakshmi
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
authors.forename: Golla
authors.initials: G
authors.lastname: Kishore
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
authors.forename: C
authors.initials: C
authors.lastname: Bhaskar
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
mesh_terms: D000282:Administration, Intravaginal; D000480:Alkynes; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018890:Chemoprevention / Q000379:methods*; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003521:Cyclopropanes; D005260:Female; D007778:Lactobacillus / Q000187:drug effects; D007781:Lactoferrin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D051381:Rats; D014627:Vaginitis / Q000139:chemically induced / Q000473:pathology
chemical_list: D000480:Alkynes; D000890:Anti-Infective Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D007781:Lactoferrin; D003474:Curcumin; C098320:efavirenz