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Development of a nanostructured hydrogel containing a papain and cyclodextrin complex

Grant number: 10/10935-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2010
Effective date (End): September 30, 2014
Field of knowledge:Engineering - Materials and Metallurgical Engineering
Principal researcher:Ademar Benévolo Lugão
Grantee:Gustavo Henrique Costa Varca
Home Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil


Papain is a proteolytic enzyme that holds debridement properties, commonly used for wound treatment. A natural unfolding mechanism, as well as incompatibilities with several substances, decreases its bioactivity and shelf life. Recently the FDA has taken an action against papain containing topical products due to severe adverse events reported in patients submitted to papain treatments, requiring registration of such products prior to their commercialization and thus, restricting the products available for these treatments. The use of radiation assures the product sterility, essential to a safe usage, induces the hydrogel crosslinking, and reduces the cytotoxic effects and the caused allergenic reactions. However, proteins are sensitive to radiation secondary effects, which may affect the final product and the application of such technique. The use of cyclodextrins for a papain and cyclodextrin complex formation, may provide suitable radiolysis resistance, reduce the enzyme hydrolysis sensitivity and slow the unfolding mechanism, thus guaranteeing a suitable and effective product. The present work aims to develop a nanostructured polyvinilpirrolidone hydrogel containing a papain and cyclodextrin complex as an attempt to produce a suitable and reliable medicine for wound and eschar treatments. The samples will be exposed to gamma radiation at the sterilizing dose of 25 kGy, using a 60CO source. Physico-chemical, morphological and biological characterizations of the complex and the final product will be performed as an attempt to evaluate the properties conferred by the cyclodextrin to the enzyme, over its biological activity, allergenic and cytotoxic effects, with and without radiation, as well as characterize the final product. (AU)

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Scientific publications (4)
(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)
SOWINSKI, SEBASTIAN; VARCA, GUSTAVO H. C.; KADLUBOWSKI, SLAWOMIR; LUGAO, ADEMAR B.; ULANSKI, PIOTR. A mechanistic approach towards the formation of bityrosine in proteins by ionizing radiation-GYG model peptide. Radiation Physics and Chemistry, v. 188, NOV 2021. Web of Science Citations: 0.
CORAZZA, FULVIO G.; ERNESTO, V, JULIA; NAMBU, FELIPE A. N.; DE CARVALHO, LUMA R.; LEITE-SILVA, VANIA R.; VARCA, GUSTAVO H. C.; CALIXTO, LEANDRO A.; VIEIRA, DANIEL P.; ANDREO-FILHO, NEWTON; LOPES, PATRICIA S. Papain-cyclodextrin complexes as an intestinal permeation enhancer: Permeability and in vitro safety evaluation. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 55, FEB 2020. Web of Science Citations: 0.
VARCA, G. H. C.; KADLUBOWSKI, S.; WOLSZCZAK, M.; LUGAO, A. B.; ROSIAK, J. M.; ULANSKI, P. Synthesis of papain nanoparticles by electron beam irradiation - A pathway for controlled enzyme crosslinking. International Journal of Biological Macromolecules, v. 92, p. 654-659, NOV 2016. Web of Science Citations: 2.
VARCA, GUSTAVO H. C.; PEROSSI, GABRIELA G.; GRASSELLI, MARIANO; LUGAO, ADEMAR B. Radiation synthesized protein-based nanoparticles: A technique overview. Radiation Physics and Chemistry, v. 105, p. 48-52, DEC 2014. Web of Science Citations: 4.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
. Development of a nanostructured hydrogel containing papain and cyclodextrin complex. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT) São Paulo.

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Filed patent(s) as a result of this research project

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020130050342 - Comissão Nacional De Energia Nuclear (CNEN) ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - March 2013, 01