Targeted Delivery of PSC-RANTES for HIV-1 Prevention using Biodegradable Nanoparticles

Abstract

Purpose Nanoparticles formulated from the biodegradable co-polymer poly(lactic-co-glycolic acid) (PLGA), were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting for PSC-RANTES anti-HIV-1 activity. Materials and Methods PSC-RANTES nanoparticles formulated via a double emulsion process and characterized in both in vitro and ex vivo systems to determine PSC-RANTES release rate, nanoparticle tissue permeation, and anti-HIV bioactivity. Results Spherical, monodisperse (PDI = 0.098 ± 0.054) PSC-RANTES nanoparticles (d = 256.58 ± 19.57 nm) with an encapsulation efficiency of 82.23 ± 8.35% were manufactured. In vitro release studies demonstrated a controlled release profile of PSC-RANTES (71.48 ± 5.25% release). PSC-RANTES nanoparticle maintained comparable anti-HIV activity with unformulated PSC-RANTES in a HeLa cell-based system with an IC50 of approximately 1pM. In an ex vivo cervical tissue model, PSC-RANTES nanoparticles displayed a fivefold increase in tissue uptake, enhanced tissue permeation, and significant localization at the basal layers of the epithelium over unformulated PSC-RANTES. Conclusions These results indicate that PSC-RANTES can readily be encapsulated into a PLGA nanoparticle drug delivery system, retain its anti-HIV-1 activity, and deliver PSC-RANTES to the target tissue. This is crucial for the success of this drug candidate as a topical microbicide product.

Safety and Pharmacokinetics of Quick-Dissolving Polymeric Vaginal Films Delivering the Antiretroviral IQP-0528 for Preexposure Prophylaxis

“…PLGA-based encapsulation of nanoparticles is widely used for drug delivery because of its biodegradability, allowing its reabsorption by the body and, hence, lowering toxicity (83). PLGA nanoparticles have been demonstrated to intravaginally deliver small interfering RNA (siRNA) and Rantes (58,81). Therefore, the incorporation of nanoparticle encapsulation into a microbicide formulation has the potential to confer long-term protection from a single dose.…”

Polyethylene Glycol-Based Hydrogels for Controlled Release of the Antimicrobial Subtilosin for Prophylaxis of Bacterial Vaginosis

“…Therefore, there is a need for developing alternative vaginal drug delivery systems for application as microbicides. Temperatureand pH-sensitive hydrogels and nanoparticles are currently being explored as potential microbicide delivery systems (55)(56)(57)(58).…”

Nanobiotechnology Solutions againstAedes aegypti

“…41 However, in other studies, PLA NPs were demonstrated to be feasible drug delivery carriers to enhance tissue uptake and the targeting of other macromolecules with anti-HIV-1 activity. 42 Also, PLGA nanoparticles have shown interesting applications as vaccine-delivery vehicles for treatment of viral infections. 43 Polyhexylcyanoacrylate nanoparticles were loaded with saquinavir (another HIV protease inhibitor) or zalcitabine (a nucleoside analog) and tested under in vitro conditions in primary human monocytes/macrophages.…”