Nanoparticle Encapsulation for Antiretroviral Pre-Exposure Prophylaxis

Abstract

HIV continues to be one of the greatest challenges facing the global health community. More than 36 million people currently live with HIV and, in 2015 2.1 million new infections were reported globally. Pre-Exposure Prophylaxis (PrEP) prevents HIV infection by inhibiting viral entry, replication, or integration at the primary site of pathogenic contraction. Failures of large antiretroviral drug (ARV) PrEP clinical trials indicate the current insufficiencies of PrEP for women in high-risk areas, such as sub-Saharan Africa. A combination of social, adherence, and drug barriers create these insufficiencies and limit the efficacy of ARV. Nanotechnology offers the promise of extended drug release and enhances bioavailability of ARVs when encapsulated in polymeric nano-particles. Nanoparticle encapsulation has been evaluated in vitro in comparative studies to drug solutions and exhibit higher efficacy and lower cytotoxicity profiles. Delivery systems for nanoparticle PrEP facilitate administration of nano-encapsulated ARVs to high-risk tissues. In this mini-review, we summarize the comparative nanoparticle and drug solution studies and the potential of two delivery methods: thermosensitive gels and polymeric nanoparticle films for direct prophylactic applications.

Figure 1

Fabrication of thermosensitive gel with NP-encapsulated ARVs for vaginal application of PrEP to high-risk tissues. ARVs encapsulated in polymeric nano-particles using oil-in-water emulsion technique with the organic phase comprised of ARVs, DMSO, N-methyl-pyrrolidone, and ethyl acetate emulsified in ultrapure water. ARV-NPs are prepared in a citrate buffer with the addition of Plurionic F127 and F68 at a 20:1 ratio to the buffer for gelation. The solution is set overnight in a cooled environment. pH modifications are made for CAP-NP and PLGA-ARV-NP fabrications along with glycerol addition. Black-NPs, Red: ARVs, Blue: polymer^[38].

Figure 2

Fabrication of polymeric film with NP-encapsulated ARVs embedded into film for vaginal application of PrEP to high-risk tissues. Polymeric excipients HPMC and PVA were combined at a 4:1 ratio in a solution to 3% w/w of water containing 90% excipient polymers and 10% additional glycerin. ARV encapsulated PLGA NPs were added to the polymer-glycerin solution immediately before casting in 12 cm X 12 cm polystyrene molds^[–73].