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Study of activity of soluble hyaluronidases or encapsulated in association or not with MK886

Grant number: 07/04741-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2008
Effective date (End): May 31, 2011
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Lúcia Helena Faccioli
Grantee:Claudia da Silva Bitencourt
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:05/54855-0 - Animal toxins: structure, function and biotechnological applications, AP.TEM


Venoms and toxins produced by animals are important to knowledge of human physiology and are formed by complex moisture of proteins. After a bitten, these compounds may induce loss of tissue integrity by miotoxins, metaloproteases and hialuronidases. Hyaluronidases are spreading factors in venoms because they facilitate toxin diffusion into the tissues, thus contributing to systemic envenomation. The biologic functions of hialuronidases are the alteration of the structure and functions of extracellular matrix and increase drugs absorption. Hyaluronidases have been employed therapeutically in order to increase the speed of absorption; to reduce discomfort due intramuscular injection of fluid; to increase the effectiveness of local anesthetics and to treat acute myocardial infarction. Nowadays the association of hialuronidase and antitumoral drugs for cancer therapy is a great concern. Diverse studies recently published in the literature show the relation between inflammatory mediators and carcinogenesis. Leukotrienes, mediators inflammatory, are known to be involved in the promotion, progress and metastasis of tumors. The inhibition of activation of the 5-lipoxygenase enzyme probably is a strategy for the cancer therapy. MK886 is an inhibitor of leukotriene biosynthesis and this inhibition is mediated by interaction with 5-lipoxygenase activating protein (FLAP). Due to increased mortality by cancer, especially lung cancer, a new therapeutic approach is necessary. In this context, the aim of the present study is the development of microspheres with MK886 and hialuronidase. We hypothesized that hyaluronidase will alter the extracelluar matrix, releasing MK 886 next to the tumor. Moreover, microspheres promote a controlled liberation of these compounds. The work will be performed in two stages: First, the characterization of proinflammatory activity of soluble hialuronidases isolated of venom of Crotalus durissus terrificus and Tityus serrulatus will be performed. Second, the formulation of microspheres of polimers with hyaluronidase and with or without MK886 will be prepared. The microspheres will be evaluated in vitro, using tumoral cells culture, as well as in vivo after intratracheal inoculation. The data that will be obtained by the present study will provide information about hyaluronidase, and help to propose a new therapeutic approach to tumors. The results will be published in periods with significantly impact.

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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)
PEREIRA, PRISCILLA A. T.; BITENCOURT, CLAUDIA S.; REIS, MOUZARLLEM B.; FRANTZ, FABIANI G.; SORGI, CARLOS A.; SOUZA, CAMILA O. S.; SILVA, CELIO L.; GARDINASSI, LUIZ G.; FACCIOLI, LUCIA H. Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation. Inflammation Research, v. 69, n. 1 NOV 2019. Web of Science Citations: 0.
BITENCOURT, CLAUDIA DA SILVA; DA SILVA, LETICIA BUENO; TARTARI PEREIRA, PRISCILLA APARECIDA; GELFUSO, GUILHERME MARTINS; FACCIOLI, LUCIA HELENA. Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 136, p. 678-686, DEC 1 2015. Web of Science Citations: 10.

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