Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

Autor: Akhavein N; ViiV Healthcare, Five Moore Drive, Research Triangle Park, NC, 27709, USA. nima.2.akhavein@viivhealthcare.com., Baum MM; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Gunawardana M; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Moss JA; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Calvez S; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Remedios-Chan M; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Fanter R; Department of Chemistry, Oak Crest Institute of Science, 128‑132 W. Chestnut Ave., Monrovia, CA, 91016, USA., Lenhard S; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA., Rusk S; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA.; Janssen, 200 Great Valley Parkway, Malvern, PA, 19355, USA., Azzarano L; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA., McCoy D; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA., Jucker B; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA., Johns B; ViiV Healthcare, Five Moore Drive, Research Triangle Park, NC, 27709, USA.; HemoShear, 501 Locust Ave, Charlottesville, VA, 22902, USA., Burke M; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426, USA.; Stemline Therapeutics, 750 Lexington Avenue, 11th Floor, New York, NY, 10022, USA., Velthuisen E; ViiV Healthcare, Five Moore Drive, Research Triangle Park, NC, 27709, USA.; HemoShear, 501 Locust Ave, Charlottesville, VA, 22902, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 May 21; Vol. 14 (1), pp. 11573. Date of Electronic Publication: 2024 May 21.
DOI: 10.1038/s41598-024-58583-w
Abstrakt: 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's 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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