Abstract

Here we report an ultra-long-acting tunable, biodegradable, and removable polymer-based delivery system that offers sustained drug delivery for up to one year for HIV treatment or prophylaxis. This robust formulation offers the ability to integrate multiple drugs in a single injection, which is particularly important to address the potential for drug resistance with monotherapy. Six antiretroviral drugs were selected based on their solubility in N-methyl-2-pyrrolidone and relevance as a combination therapy for HIV treatment or prevention. All drugs released with concentrations above their protein-adjusted inhibitory concentration and retained their physical and chemical properties within the formulation and upon release. The versatility of this formulation to integrate multiple drugs and provide sustained plasma concentrations from several weeks to up to one year, combined with its ability to be removed to terminate the treatment if necessary, makes it attractive as a drug delivery platform technology for a wide range of applications.

Details

Title
Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery
Author
S Rahima Benhabbour 1 ; Kovarova, Martina 2 ; Jones, Clinton 3 ; Copeland, Daijha J 3   VIAFID ORCID Logo  ; Shrivastava, Roopali 4 ; Swanson, Michael D 2 ; Sykes, Craig 5 ; Ho, Phong T 2 ; Cottrell, Mackenzie L 2 ; Sridharan, Anush 4 ; Fix, Samantha M 3 ; Thayer, Orrin 2   VIAFID ORCID Logo  ; Long, Julie M 2 ; Hazuda, Daria J 6 ; Dayton, Paul A 4 ; Mumper, Russell J 7 ; Kashuba, Angela D M 5 ; Garcia, J Victor 2   VIAFID ORCID Logo 

1  UNC_NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, Chapel Hill, NC, USA 
2  International Center for the Advancement of Translational Science, Division of Infectious Diseases, Center for Aids Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 
3  UNC Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, Chapel Hill, NC, USA 
4  UNC_NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 
5  Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 
6  Infectious Disease Biology, Merck Research Laboratories, West Point, PA, USA 
7  University of Georgia, Office of the Provost, Athens, GA, USA 
Pages
1-12
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12141-5
ProQuest document ID
2294471163
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.