Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention
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 pl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/14/6/1196 |
| _version_ | 1797443224370937856 |
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| author | Xin Tong Sravan Kumar Patel Jing Li Dorothy Patton Elaine Xu Peter L. Anderson Urvi Parikh Yvonne Sweeney Julie Strizki Sharon L. Hillier Lisa C. Rohan |
| author_facet | Xin Tong Sravan Kumar Patel Jing Li Dorothy Patton Elaine Xu Peter L. Anderson Urvi Parikh Yvonne Sweeney Julie Strizki Sharon L. Hillier Lisa C. Rohan |
| author_sort | Xin Tong |
| collection | DOAJ |
| description | 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, <i>Lactobacillus</i> 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 (IC<sub>50</sub> 0.46 vs. 0.54 nM) and were found to have no impact on <i>Lactobacillus</i>. 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. |
| first_indexed | 2024-03-09T12:52:54Z |
| format | Article |
| id | doaj.art-6bf3f732d9d1404da37bb79dfae40c79 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T12:52:54Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-6bf3f732d9d1404da37bb79dfae40c792023-11-30T22:03:52ZengMDPI AGPolymers2073-43602022-03-01146119610.3390/polym14061196Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV PreventionXin Tong0Sravan Kumar Patel1Jing Li2Dorothy Patton3Elaine Xu4Peter L. Anderson5Urvi Parikh6Yvonne Sweeney7Julie Strizki8Sharon L. Hillier9Lisa C. Rohan10Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USAMagee-Womens Research Institute, Pittsburgh, PA 15213, USADepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USAMerck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USAMagee-Womens Research Institute, Pittsburgh, PA 15213, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USAMK-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, <i>Lactobacillus</i> 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 (IC<sub>50</sub> 0.46 vs. 0.54 nM) and were found to have no impact on <i>Lactobacillus</i>. 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.https://www.mdpi.com/2073-4360/14/6/1196nanomedicinevaginal drug deliveryHIV/AIDSantiretroviralnonhuman primates |
| spellingShingle | Xin Tong Sravan Kumar Patel Jing Li Dorothy Patton Elaine Xu Peter L. Anderson Urvi Parikh Yvonne Sweeney Julie Strizki Sharon L. Hillier Lisa C. Rohan Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention Polymers nanomedicine vaginal drug delivery HIV/AIDS antiretroviral nonhuman primates |
| title | Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention |
| title_full | Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention |
| title_fullStr | Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention |
| title_full_unstemmed | Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention |
| title_short | Development and Evaluation of Nanoparticles-in-Film Technology to Achieve Extended In Vivo Exposure of MK-2048 for HIV Prevention |
| title_sort | development and evaluation of nanoparticles in film technology to achieve extended in vivo exposure of mk 2048 for hiv prevention |
| topic | nanomedicine vaginal drug delivery HIV/AIDS antiretroviral nonhuman primates |
| url | https://www.mdpi.com/2073-4360/14/6/1196 |
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