{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:17:24Z","timestamp":1793146644303,"version":"4.5.0"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound\u2019s physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.<\/jats:p>","DOI":"10.1038\/s41598-024-58583-w","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T11:02:01Z","timestamp":1716289321000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug"],"prefix":"10.1038","volume":"14","author":[{"given":"Nima","family":"Akhavein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc M.","family":"Baum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjula","family":"Gunawardana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Calvez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Remedios-Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Fanter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Lenhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Rusk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Azzarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"McCoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Jucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Johns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Velthuisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"58583_CR1","unstructured":"Prevailing against Pandemics by Putting People at the Centre\u2014World AIDS Day Report 2020, UNAIDS, pp. 92 (2020)."},{"key":"58583_CR2","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1002\/cpt.1227","volume":"104","author":"CW Hendrix","year":"2018","unstructured":"Hendrix, C. W. HIV antiretroviral pre-exposure prophylaxis: Development challenges and pipeline promise. Clin. Pharmacol. Ther. 104, 1082\u20131097 (2018).","journal-title":"Clin. Pharmacol. Ther."},{"key":"58583_CR3","unstructured":"Diagnoses of HIV Infection in the United States and Dependent Areas, 2018 (Updated), Centers for Disease Control and Prevention (2018)."},{"key":"58583_CR4","unstructured":"Estimated HIV Incidence and Prevalence in the United States 2010\u20132016, Centers for Disease Control and Prevention (2019)."},{"key":"58583_CR5","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s13346-017-0391-6","volume":"7","author":"WR Lykins","year":"2017","unstructured":"Lykins, W. R., Luecke, E., Johengen, D., van der Straten, A. & Desai, T. A. Long acting systemic HIV pre-exposure prophylaxis: An examination of the field. Drug Deliv. Transl. Res. 7, 805\u2013816 (2017).","journal-title":"Drug Deliv. Transl. Res."},{"key":"58583_CR6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz938","author":"E DeJesus","year":"2019","unstructured":"DeJesus, E. et al. A phase IIa study evaluating safety, pharmacokinetics, and antiviral activity of GSK2838232, a novel, second-generation maturation inhibitor, in participants with human immunodeficiency virus type 1 infection. Clin. Infect. Dis. https:\/\/doi.org\/10.1093\/cid\/ciz938 (2019).","journal-title":"Clin. Infect. Dis."},{"key":"58583_CR7","unstructured":"J.L. Jeffrey, P. Wang, C. McDanal, P.J. Shipper, K. Brown, C. Galardi, J. Tang, M. Nijhuis, B.A. Johns, GSK2838232, a Second Generation HIV-1 Maturation Inhibitor with an Optimized virology profile. In Conference on Retroviruses and Opportunistic Infections (CROI), CROI, pp. 538 (2015)."},{"key":"58583_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.408","volume":"6","author":"M Johnson","year":"2018","unstructured":"Johnson, M. et al. The safety, tolerability, and pharmacokinetic profile of GSK2838232, a novel 2nd generation HIV maturation inhibitor, as assessed in healthy subjects. Pharmacol. Res. Perspect. 6, e00408 (2018).","journal-title":"Pharmacol. Res. Perspect."},{"key":"58583_CR9","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1093\/cid\/ciz938","volume":"71","author":"E DeJesus","year":"2020","unstructured":"DeJesus, E. et al. A phase IIa study evaluating safety, pharmacokinetics, and antiviral activity of GSK2838232, a novel, second-generation maturation inhibitor, in participants with human immunodeficiency virus type 1 infection. Clin. Infect. Dis. 71, 1255\u20131262 (2020).","journal-title":"Clin. Infect. Dis."},{"key":"58583_CR10","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1002\/cpdd.820","volume":"9","author":"M Johnson","year":"2020","unstructured":"Johnson, M. et al. A phase 1 study to assess the relative bioavailability, food effect, and safety of a tablet formulation of GSK2838232, a novel HIV maturation inhibitor in healthy participants after single and repeated doses. Clin. Pharmacol. Drug Dev. 9, 972\u2013977 (2020).","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"58583_CR11","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1128\/AAC.00656-15","volume":"59","author":"M Gunawardana","year":"2015","unstructured":"Gunawardana, M. et al. Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis. Antimicrob. Agents Chemother. 59, 3913\u20133919 (2015).","journal-title":"Antimicrob. Agents Chemother."},{"key":"58583_CR12","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. Guide for the Care and Use of Laboratory Animals 8th edn. (The National Academies Press, 2011).","edition":"8"},{"key":"58583_CR13","doi-asserted-by":"publisher","first-page":"569373","DOI":"10.3389\/fphar.2020.569373","volume":"11","author":"M Gunawardana","year":"2020","unstructured":"Gunawardana, M. et al. Multispecies evaluation of a long-acting tenofovir alafenamide subdermal implant for HIV prophylaxis. Front. Pharmacol. 11, 569373 (2020).","journal-title":"Front. 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