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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 6
[1] Univ Sao Paulo, Dept Pharmacol, Inst Ciencias Biomed, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: International Journal of Pharmaceutics; v. 585, JUL 30 2020.
Web of Science Citations: 0

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)

FAPESP's process: 17/04174-4 - Development and evaluation of cationic bioadhesive nanocarriers as a platform to localize piplartine in the breast for tumor treatment
Grantee:Vanessa Franco Carvalho Dartora
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/05038-0 - Effect of environmental enrichment on resilience to chronic unpredictable stress: epigenetic regulation of the BDNF gene and consequences on ethanol consumption
Grantee:Rosana Camarini
Support type: Regular Research Grants
FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
Grantee:Luciana Biagini Lopes
Support type: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue
Grantee:Luciana Biagini Lopes
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 18/18813-1 - Bioresponsive gels containing nanoparticles for exudate control and co-delivery of propranolol and adenosine for wound healing applications
Grantee:Jenyffer Kelly Rocha de Matos
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 15/02397-0 - Study of environmental enrichment inducing a protective phenotype of behaviors that assess addictive features in mice
Grantee:Rosana Camarini
Support type: Regular Research Grants