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Poloxamer-hyaluronic acid hydrogels as sulforaphane delivery systems for the osteoarthritis treatment

Grant number: 15/14763-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2016
Effective date (End): January 31, 2019
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Daniele Ribeiro de Araujo
Grantee:Mônica Helena Monteiro Do Nascimento
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Associated research grant:14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics, AP.TEM


Sulforaphane (SFN) is an isothiocyanates-drug member which presents anti-inflammatory action as well as anti-carcinogenic properties. Different studies have reported also anti-arthritic and immunoregulatory activities, since SFN is capable of inhibit the synovial hyperplasia and the proliferation of activated T cells. These results highlight the possibility of the therapeutic use of the SFN for the treatment of osteoarthritis (OA). OA is a chronic, degenerative disease that commonly affects the weight-bearing joints, where the treatment aims to evoke the pain and inflammation relief, and to block the bone loss. The local therapy, such as the intra-articular injection is one of effective measures to relief the symptoms and prevent the progression of OA. Although the use of the needle is not removed from the pharmacotherapeutic regimen, the intra-articular injection favors the drug permanence in the site of action, thereby minimizing systemic side effects of conventionally administered drugs (such as orally, for example). Thus, the combination of thermoreversible properties inherent to the poloxamers and biocompatibility / biodegradability of hyaluronic acid, favor the development of osteotropic pharmaceutical formulations for new drugs, such as sulforaphane. Therefore, this proposal aims to prepare, to characterize and to evaluate the biocompatibility and the in vitro efficacy of poloxamer-hyaluronic acid hybrid hydrogels as delivery systems for intraarticular release of sulforaphane, on the treatment of OA. The physico-chemical characterization of the systems will be performed regarding to the micelle diameter, temperature and thermodynamics of micellization process, sol-gel transition temperature, rheological properties, in vitro dissolution and release. The in vitro biocompatibility and efficacy will be assessed by morphological analysis and cell viability as well as by detecting molecular markers (type II collagen, matrix metalloproteinases 1, 3 and 13-type and interleukin-10, Nuclear factor º-B) in chondrocytes after stimulation with interleukin-1².

Scientific publications
(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)
NASCIMENTO, M. H. M.; FRANCO, M. K. K. D.; YOKAICHYIA, F.; DE PAULA, E.; LOMBELLO, C. B.; DE ARAUJO, D. R. Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release. International Journal of Biological Macromolecules, v. 111, p. 1245-1254, MAY 2018. Web of Science Citations: 11.

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