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 IC(50) 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.
PURPOSE: Nanoparticles formulated from the biodegradable co-polymerpoly(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 IC(50) 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.
Authors: V S Torre; A J Marozsan; J L Albright; K R Collins; O Hartley; R E Offord; M E Quiñones-Mateu; E J Arts Journal: J Virol Date: 2000-05 Impact factor: 5.103
Authors: D E Mosier; G R Picchio; R J Gulizia; R Sabbe; P Poignard; L Picard; R E Offord; D A Thompson; J Wilken Journal: J Virol Date: 1999-05 Impact factor: 5.103
Authors: Catherine M Finnegan; Satinder S Rawat; Anu Puri; Ji Ming Wang; Francis W Ruscetti; Robert Blumenthal Journal: Proc Natl Acad Sci U S A Date: 2004-10-15 Impact factor: 11.205
Authors: José das Neves; Johan Michiels; Kevin K Ariën; Guido Vanham; Mansoor Amiji; Maria Fernanda Bahia; Bruno Sarmento Journal: Pharm Res Date: 2011-11-10 Impact factor: 4.200
Authors: Anita Leporati; Mikhail S Novikov; Vladimir T Valuev-Elliston; Sergey P Korolev; Anastasia L Khandazhinskaya; Sergey N Kochetkov; Suresh Gupta; Julian Goding; Elijah Bolotin; Marina B Gottikh; Alexei A Bogdanov Journal: Nanomedicine Date: 2016-07-25 Impact factor: 5.307