2. Academic Validation
  3. Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention

Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention

  • Polymers (Basel). 2022 Mar 16;14(6):1196. doi: 10.3390/polym14061196.
Xin Tong 1 2,  Sravan Kumar Patel 1 2,  Jing Li 1 2,  Dorothy Patton 3,  Elaine Xu 1 2,  Peter L Anderson 4,  Urvi Parikh 2,  Yvonne Sweeney 3,  Julie Strizki 5,  Sharon L Hillier 2 6,  Lisa C Rohan 1 2 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • 2 Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
  • 3 Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
  • 4 Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA.
  • 5 Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • 6 Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
PMID: 35335526 DOI: 10.3390/polym14061196
Abstract

MK-2048 is a second-generation integrase inhibitor active against HIV, which has been applied vaginally using ring formulations. In this work, a nanoparticle-in-film technology was developed as a discrete pre-exposure prophylactic product option against HIV for an extended duration of use. A film platform loaded with poly (lactic-co-glycolic acid) nanoparticles (PNP) encapsulating MK-2048 was engineered. MK-2048 PNPs were loaded into films that were manufactured via the solvent casting method. Physicochemical and mechanical properties, in vitro efficacy, Lactobacillus compatibility, in vitro and ex vivo permeability, and in vivo pharmacokinetics in macaques were evaluated. PNPs with a mean diameter of 382.2 nm and −15.2 mV zeta potential were obtained with 95.2% drug encapsulation efficiency. PNP films showed comparable in vitro efficacy to free MK-2048 (IC50 0.46 vs. 0.54 nM) and were found to have no impact on Lactobacillus. MK-2048 encapsulated in PNPs showed an increase in permeability (>4-fold) compared to the free MK-2048 in MDCKII cell lines. Furthermore, PNPs had higher ectocervical tissue permeability (1.7-fold) compared to free MK-2048. PNP films showed sustained drug levels for at least 3 weeks in the macaque vaginal fluid. This work demonstrates the synergy of integrating nanomedicine and polymeric film technology to achieve sustained vaginal drug delivery.

Keywords

HIV/AIDS; antiretroviral; nanomedicine; nonhuman primates; vaginal drug delivery.

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