Development of nanostructured systems to increase the efficacy of chemotherapy and immunotherapy for Bladder Cancer

• Grant number: 19/01315-1
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2019
• Effective date (End): February 28, 2022
• Field of knowledge: Engineering - Materials and Metallurgical Engineering
• Principal researcher: Ademar Benévolo Lugão
• Grantee: Caroline Santos Alves de Lima
• Home Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 21/09636-1 - DEVELOPMENT OF MUCOADHESIVE HYDROGELS CONTAINING PAPAIN FOR GEMCITABINE LOADING, BE.EP.DR

Abstract

Bladder Cancer is a disease that affects a large part of the population leading to serious harm to public health. Treatment of Bladder Cancer is primarily performed by transurethral resection to remove the visible tumor, followed by immunosuppression or intravesical chemotherapy, according to the stage of the disease. However, the instillation of drugs in the human bladder presents some challenges, such as the permeation of the active substance in the urothelium - which is a highly impermeable tissue - and the residence time of this drug, which is limited due to the presence of the urine that ends up diluting it and washing it thoroughly. Thus, the main objective of this project is to develop strategies to increase adherence, permeation, residence time and specificity of intravesical chemotherapy through the application of mucoadhesive hydrogels for the administration of chemotherapeutic and/or immunotherapeutic drugs, such as gemcitabine and BCG. The gold nanoparticles coated with papain will be added to the gel in order to favor the permeation of the chemo or immunotherapeutic. It is proposed to use hydrogels based on natural polymers chitosan, gellan gum and microcellulose, already widely applied in the biomedical area, due to properties such as absence of toxicity, high biocompatibility and biodegradability. Hydrogels will be studied and evaluated for their mucoadhesiveness and gelling ability, in order to verify their adequacy to the specific treatment demands. The interactions between the pharmaceutical form and the nanoparticles will also be analyzed. Biological assays will be carried out in accordance with international standards to provide specific knowledge about the biocompatibility of the material, thus allowing a future safe clinical use. Finally, we want to develop a system with specific properties capable of decreasing the drug loading administered to the patients, reducing toxicity and side effects while increasing the residence time and permeation of the active as an alternative to the available therapies. (AU)