Agradecimentos: This work was supported by Fund?ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grants 2006/00121-9, 2010/11475-1, 2010/13088-5) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grants 487619/2012-9, 300952/2010-4, 309612/2013-6)

In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity,...

In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407-PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug-micelle interaction studies showed the formation of PL 407-PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407-PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%-45% of the gel dissolved, reaching similar to 80%-90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower K-rel values were observed for PL 407 (20%, K-rel = 112.9 +/- 10.6 mu g . h(-1/2)) and its binary systems PL 407-PL 188 (25%-5% and 25%-10%, K-rel = 80.8 +/- 6.1 and 103.4 +/- 8.3 mu g.h(-1/2), respectively) in relation to TR solution (K-rel = 417.9 +/- 47.5 mu g.h(-1/2), P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes) and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects (>72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain

Resumo:

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP

2006/00121-9; 2010/11475-1; 2010/13088-5

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ

487619/2012-9; 300952/2010-4; 309612/2013-6

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