Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery

S. Rahima Benhabbour (), Martina Kovarova, Clinton Jones, Daijha J. Copeland, Roopali Shrivastava, Michael D. Swanson, Craig Sykes, Phong T. Ho, Mackenzie L. Cottrell, Anush Sridharan, Samantha M. Fix, Orrin Thayer, Julie M. Long, Daria J. Hazuda, Paul A. Dayton, Russell J. Mumper, Angela D. M. Kashuba and J. Victor Garcia ()
Additional contact information
S. Rahima Benhabbour: University of North Carolina at Chapel Hill
Martina Kovarova: University of North Carolina at Chapel Hill
Clinton Jones: Division of Pharmacoengineering and Molecular Pharmaceutics
Daijha J. Copeland: Division of Pharmacoengineering and Molecular Pharmaceutics
Roopali Shrivastava: University of North Carolina at Chapel Hill
Michael D. Swanson: University of North Carolina at Chapel Hill
Craig Sykes: University of North Carolina at Chapel Hill
Phong T. Ho: University of North Carolina at Chapel Hill
Mackenzie L. Cottrell: University of North Carolina at Chapel Hill
Anush Sridharan: University of North Carolina at Chapel Hill
Samantha M. Fix: Division of Pharmacoengineering and Molecular Pharmaceutics
Orrin Thayer: University of North Carolina at Chapel Hill
Julie M. Long: University of North Carolina at Chapel Hill
Daria J. Hazuda: Merck Research Laboratories
Paul A. Dayton: University of North Carolina at Chapel Hill
Russell J. Mumper: University of Georgia, Office of the Provost
Angela D. M. Kashuba: University of North Carolina at Chapel Hill
J. Victor Garcia: University of North Carolina at Chapel Hill

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12141-5

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