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Development and pharmacological evaluation of drug-delivery systems containing tramadol in thermoreversible hydrogels for pain treatment

Abstract

Despite is not a new opioid analgesic, tramadol has been used for acute and chronic pain management due to its particular mechanism of action, involving effective analgesia (but presenting short duration of action) and low incidence of adverse effects compared to classical opioids (such as morphine and fentanyl). In this manner, the development of controlled release systems containing tramadol would be of great interest for studying new formulations with potential clinical use, favoring the administration and prolonging the duration of action. Among the different carriers, micelles consisting of co-polymers named poloxamers have been studied for many purposes. Poloxamers (composed of basic units of polyoxiethylene, polyoxipropylene and polyoxiethylene) have been investigated as drug delivery systems presenting promising results in terms of improved biopharmaceutical, pharmacodynamic and pharmacokinetic properties. One of most important advantages is the the capability (when at concentrated solutions) of forming hydrogels at temperatures closed to the human body (sol-gel transition), making them effective base for hydrogels, emulsions, nanoparticles, as well as favoring parenteral administration and controlling the release of drugs for a long time. Therefore, this purpose aims to prepare, to characterize, to evaluate the cytotoxicity (using erythrocytes as membrane models) and the therapeutic efficacy of controlled release formulations containing tramadol in thermorreversible co-polymeric hydrogels (such as poloxamer 407, poloxamer 188 and poloxamer 403, isolated or as binary systems) for subcutaneous injection, looking forward the treatment of pain. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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. Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 10, p. 2391-2401, 2015. Web of Science Citations: 18.
OSHIRO, ALISSON; DA SILVA, DEYSE C.; DE MELLO, JOYCE C.; DE MORAES, VIVIAN W. R.; CAVALCANTI, LEIDE P.; FRANCO, MARGARETH K. K. D.; ALKSCHBIRS, MELISSA I.; FRACETO, LEONARDO F.; YOKAICHIYA, FABIANO; RODRIGUES, TIAGO; DE ARAUJO, DANIELE R. Pluronics F-127/L-81 Binary Hydrogels as Drug-Delivery Systems: Influence of Physicochemical Aspects on Release Kinetics and Cytotoxicity. Langmuir, v. 30, n. 45, p. 13689-13698, NOV 18 2014. Web of Science Citations: 24.
DE ARAUJO, DANIELE R.; DA SILVA, DEYSE C.; BARBOSA, RAQUEL M.; FRANZ-MONTAN, MICHELLE; CEREDA, CINTIA M. S.; PADULA, CRISTINA; SANTI, PATRIZIA; DE PAULA, ENEIDA. Strategies for delivering local anesthetics to the skin: focus on liposomes, solid lipid nanoparticles, hydrogels and patches. Expert Opinion on Drug Delivery, v. 10, n. 11, p. 1551-1563, NOV 2013. Web of Science Citations: 31.
VOLOBUEF, CRISTIANE; MORAES, CAROLINA M.; NUNES, LAZARO A. S.; CEREDA, CINTIA M. S.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K. K. D.; BRAGA, ANGELICA F. A.; DE PAULA, ENEIDA; TOFOLI, GIOVANA RADOMILLE; FRACETO, LEONARDO F.; DE ARAUJO, DANIELE R. Sufentanil-2-hydroxypropyl-beta-cyclodextrin inclusion complex for pain treatment: Physicochemical, cytotoxicity, and pharmacological evaluation. Journal of Pharmaceutical Sciences, v. 101, n. 10, p. 3698-3707, OCT 2012. Web of Science Citations: 6.
SANTOS DE SOUZA, ANA CAROLINA; JUSTO, GISELLE ZENKER; DE ARAUJO, DANIELE RIBEIRO; MARTINS CAVAGIS, ALEXANDRE D. Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 28, n. 5, p. 771-792, 2011. Web of Science Citations: 15.

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