Targeted delivery of PSC-RANTES for HIV-1 prevention using biodegradable nanoparticles.
OBJECTIVE
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.


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.
Ham
Anthony S
AS
Magee-Womens Research Institute, 204 Craft Avenue, B509, Pittsburgh, Pennsylvania, 15213, USA.
Cost
Marilyn R
MR
Sassi
Alexandra B
AB
Dezzutti
Charlene S
CS
Rohan
Lisa Cencia
LC
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000737:chemistry* / Q000493:pharmacokinetics; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D012995:Solubility; D013499:Surface Properties; D014776:Virus Cultivation
D023181:Antimicrobial Cationic Peptides; D001672:Biocompatible Materials; D018946:Chemokine CCL5; D004337:Drug Carriers; D023581:HIV Fusion Inhibitors; C492865:RANTES, N(alpha)-(n-nonanoyl)-desSer(1)-(thioproline(2),cyclohexylglycine(3))-; C045866:peptide-Gly-Leu-amide