Development of a nanostructured hydrogel containing a papain and cyclodextrin complex

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

Abstract

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)

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)

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. (10/10935-9, 15/09822-9)

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. (10/10935-9)

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. (10/10935-9)

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. (15/19212-3, 10/10935-9, 16/22916-5, 15/19213-0)

CORAZZA, FULVIO G.; ERNESTO, JULIA V.; NAMBU, FELIPE A. N.; CALIXTO, LEANDRO A.; VARCA, GUSTAVO H. C.; VIEIRA, DANIEL P.; LEITE-SILVA, VANIA R.; ANDREO-FILHO, NEWTON; LOPES, PATRICIA S.. Enhancing the Furosemide Permeability by Papain Minitablets Through a Triple Co-culture In Vitro Intestinal Cell Model. AAPS PHARMSCITECH, v. 21, n. 7, p. 10-pg., 2020-09-04. (10/10935-9, 16/22916-5, 15/19213-0, 15/19212-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

VARCA, Gustavo Henrique Costa. Development of a nanostructured hydrogel containing papain and cyclodextrin complex. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT) São Paulo.