Development of mucoadhesive hydrogels containing papain for gemcitabine loading

• Grant number: 21/09636-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 20, 2021
• End date: November 19, 2022
• Field of knowledge: Engineering - Materials and Metallurgical Engineering
• Principal Investigator: Ademar Benévolo Lugão
• Grantee: Caroline Santos Alves de Lima
• Supervisor: Carmen Alvarez-Lorenzo
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Universidade de Santiago de Compostela, Vida (USC), Spain
• Associated to the scholarship: 19/01315-1 - Development of nanostructured systems to increase the efficacy of chemotherapy and immunotherapy for Bladder Cancer, BP.DR

Abstract

A plethora of immuno-/chemo- therapeutics for the treatment of non-invasive bladder cancer have exhibited ineffectiveness attributed by low permeation through the urothelium and low residence time. Moreover, this is exacerbated by adverse effects requiring prolonged hospitalization and repeated treatments. Albeit new strategies of drug loading have been studied to improve the treatment efficiency, their toxicity profiles are a major challenge. The pharmacokinetics/pharmacodynamics are imperative to facilitate mucoadhesiveness in order to increase residence time, specificity, and sensitivity of drugs. Herein, we propose the development of gemcitabine encapsulated mucoadhesive hydrogels for efficient delivery. The hydrogel matrices are composed of natural and/or biodegradable polymers such as gellan gum, microcrystalline cellulose, carboxymethylcellulose and polyvinyl alcohol. These materials have already been used for the development of various biomaterials due to their biocompatibility. Papain, a protease will be used as a permeation enhancer for the formulations. The produced hydrogels will be investigated by Rheological analysis, mucoadhesive studies (in vitro and ex vivo), permeation and drug release assays to evaluate the potential of the formulations for a more efficient system to treat superficial bladder tumors. The aim is to obtain a system capable of reducing the amount of drug administered to patients, reducing toxicity, while increasing residence time and permeation of the chemotherapeutic drug as an alternative to the current standard of care. (AU)