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Sci Rep ; 14(1): 11573, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773172

RESUMEN

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.


Asunto(s)
Liberación de Fármacos , Animales , Ratas , Interacciones Hidrofóbicas e Hidrofílicas , Preparaciones de Acción Retardada , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Líquidos Iónicos/química , Ratas Sprague-Dawley , Masculino , Solubilidad , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/administración & dosificación , Antirretrovirales/química
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