Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

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Mendonca dos Santos, Ana Claudia ; Santos Akkari, Alessandra Cristina ; Silva Ferreira, Iasmin Rosanne ; Maruyama, Cintia Rodrigues ; Pascoli, Monica ; Guilherme, Viviane Aparecida ; de Paula, Eneida ; Fraceto, Leonardo Fernandes ; de Lima, Renata ; Melo, Patricia da Silva ; de Araujo, Daniele Ribeiro

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 10, p. 11-pg., 2015-01-01.

Abstract

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. (AU)

• FAPESP's process: 10/13088-5 - Drug delivery systems for tramadol in thermoreversible polymeric gels: cytotoxicity and pharmacological evaluation studies
• Grantee: Ana Cláudia Mendonça dos Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 06/00121-9 - New formulations for the controlled release of local anesthetics in dentistry: from development to clinical tests
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/11475-1 - Development and pharmacological evaluation of drug-delivery systems containing tramadol in thermoreversible hydrogels for pain treatment
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants