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

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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.

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Acknowledgments

The work presented was supported through grants from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institute of Health (AI-51649, Principle Investigator: Michael Lederman, Case Western Reserve University), the Pendleton Charitable Trust Fund, and the Irene McLenahan Young Investigator Research Fellowship. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID. We would like to thank the Department of Material Sciences and Engineering of the University of Pittsburgh for the provision of access to the electron microscopy instrumentation and for assistance with the execution of this part of the study.

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  1. Magee-Womens Research Institute, 204 Craft Avenue, B509, Pittsburgh, Pennsylvania, 15213, USA

    Anthony S. Ham, Marilyn R. Cost, Charlene S. Dezzutti & Lisa Cencia Rohan

  2. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Anthony S. Ham, Alexandra B. Sassi & Lisa Cencia Rohan

  3. Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Charlene S. Dezzutti & Lisa Cencia Rohan

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  1. Anthony S. Ham
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Correspondence to Lisa Cencia Rohan.

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Ham, A.S., Cost, M.R., Sassi, A.B. et al. Targeted Delivery of PSC-RANTES for HIV-1 Prevention using Biodegradable Nanoparticles. Pharm Res 26, 502–511 (2009). https://doi.org/10.1007/s11095-008-9765-2

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