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

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 pharmacolog...

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Bibliographic Details
Published in:	Scientific reports Vol. 14; no. 1; p. 11573
Main Authors:	Akhavein, Nima, Baum, Marc M., Gunawardana, Manjula, Moss, John A., Calvez, Sandrine, Remedios-Chan, Mariana, Fanter, Rob, Lenhard, Steve, Rusk, Samantha, Azzarano, Leonard, McCoy, Deborah, Jucker, Beat, Johns, Brian, Burke, Matt, Velthuisen, Emile
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 21-05-2024 Nature Publishing Group Nature Portfolio
Subjects:	631/154 639/166 639/301 639/925 692/700 Acids Animals Anti-HIV Agents - administration & dosage Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - pharmacology Anti-Retroviral Agents - administration & dosage Anti-Retroviral Agents - chemistry Antiretroviral agents Antiretroviral drugs Delayed-Action Preparations Drug delivery Drug delivery systems Drug Delivery Systems - methods Drug Liberation HIV HIV Infections - drug therapy HIV PrEP Human immunodeficiency virus Humanities and Social Sciences Hydrophobic and Hydrophilic Interactions Hydrophobicity Ionic liquids Ionic Liquids - chemistry Long-acting HIV treatment Male Maturation inhibitor multidisciplinary Oral administration Polyethylene glycol Proteins Rats Rats, Sprague-Dawley Science Science (multidisciplinary) Solubility Subdermal implants Sustained release drug delivery Transplants & implants Ionic liquids Long-acting HIV treatment Maturation inhibitor HIV PrEP Sustained release drug delivery Subdermal implants
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-58583-w