Bioresponsive nanostructured systems for sustained naltrexone release and treatment of alcohol use disorder: Development and biological evaluation

Autor(es)

Santos, Rogerio A. ^[1] ; Rae, Mariana ^[1] ; Dartora, Vanessa F. M. C. ^[1] ; Matos, Jenyffer K. R. ^[1] ; Camarini, Rosana ^[1] ; Lopes, Luciana B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Ciencias Biomed, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Pharmaceutics; v. 585, JUL 30 2020.
• Citações Web of Science: 0

Resumo

In this study, microemulsions capable of transforming into nanostructured hexagonal phase gels in vivo upon uptake of biological fluids for naltrexone prolonged release were investigated as a strategy for management of alcohol use disorder (AUD). Microemulsions were prepared using monoolein, tricaprylin, water and propylene glycol; after preliminary characterization, one formulation was selected, which contained 55% of monooleintricaprylin (M - 55). This microemulsion displayed size below 200 nm and Newtonian rheological behavior. Liquid crystalline gels formed in vitro upon 8 h of contact with water following a second order kinetics. After 120 h, < 50% of naltrexone was released in vitro independently on drug loading (5 or 10%). In vivo, gels formed within 24 h of M -55 subcutaneous administration, and persisted locally for over 30 days providing slow release of the fluorescent marker Alexa fluor compared to a solution. Using the conditioned place preference paradigm, a test used to measure drug's rewarding effects, a single dose of M - 55 containing 5% naltrexone reduced the time spent in the ethanol-paired compartment by 1.8-fold compared to saline; this effect was similar to that obtained with daily naltrexone injections, demonstrating the formulation efficacy and its ability to reduce dosing frequency. A more robust effect was observed following administration of M - 55 containing 10% of naltrexone, which was compatible with aversion. These results support M - 55 as a platform for sustained release of drugs that can be further explored for management of AUD to reduce dosing frequency and aid treatment adherence. (AU)

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