Polymeric nanoparticles for target delivery of drugs to renal proximal tubules

• Grant number: 22/00662-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: January 31, 2026
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Dayane Batista Tada
• Grantee: Dayane Batista Tada
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Associated researchers: Ana Paula Lemes ; Andrey dos Santos ; Denise Costa Arruda ; João Carlos Colmenero ; Katia da Conceição

Abstract

Type 2 diabetes mellitus is a chronic disease that results in dysfunctional regulation of blood glucose level and a multifactorial risk of other health problems, such as cardiovascular morbidity and mortality, and an important risk factor for chronic kidney disease. The constant increase in cases of diabetes mellitus 2 has encouraged innovative research on new drugs and treatment methods. A more recent type of treatment is based on the inhibition of sodium-glucose co-transporters (SGLT) which are intestinal cell and renal proximal tubule proteins responsible for the glucose absorption into the cell independently of insulin. While SGLT2 is only expressed in the kidney, SGLT1 is also expressed in the intestine. The encouraging results of clinical trials with the drug Sotaglioflozin, a dual SGLT1/SGLT2 inhibitor, were recently published. Despite the reduction in cardiovascular events in patients with type 2 diabetes mellitus, some adverse effects were reported, such as gastrointestinal discomfort, higher incidence of mycotic genital infections and a high occurrence of diarrhea, resulting in the rejection of the drugs by the patients. Motivated by the excellent results of clinical trials with Sotaglioflozin, this project will focus on the development of NPs for controlled release and specific delivery to the kidney, more specifically to the proximal tubules. The transport of Sotaglioflozin and its controlled release may increase the efficiency of renal inhibition of SGLT1/SGLT2 and reduce adverse effects, especially in the intestine, such as diarrhea. Three types of biopolymers were chosen, chitosan, polylactic-co-glycolic acid and pectin. Comparison of in vitro and in vivo biological responses, such as kidney targeting capacity, release kinetics, glycemic control, renal glucose excretion and toxicity will be performed by multicriteria decision-making methods to identify the most promising carrier for application in the treatment of type 2 diabetes mellitus. (AU)

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)

LIMA, ALAN KELBIS OLIVEIRA; SOUZA, LUCAS MARCELINO DOS SANTOS; REIS, GUILHERME FONSECA; TAVARES JR, ALBERTO GOMES; ARAUJO, VICTOR HUGO SOUSA; DOS SANTOS, LUCAS CARVALHO; DA SILVA, VITORIA REGINA PEREIRA; CHORILLI, MARLUS; BRAGA, HUGO DE CAMPOS; TADA, DAYANE BATISTA; et al. Synthesis of Silver Nanoparticles Using Extracts from Different Parts of the Paullinia cupana Kunth Plant: Characterization and In Vitro Antimicrobial Activity. PHARMACEUTICALS, v. 17, n. 7, p. 22-pg., 2024-07-01. (14/50928-2, 22/00662-2)

DE MACEDO, ERENILDO FERREIRA; NASCIMENTO, LUCCA SILVA; HOU, YANXIA; MATHEY, RAPHAEL; TADA, DAYANE BATISTA. Simultaneous detection of CA-125 and mesothelin by gold nanoparticles in surface plasmon resonance. SENSING AND BIO-SENSING RESEARCH, v. 43, p. 10-pg., 2023-12-05. (19/06803-4, 16/07354-0, 22/00662-2, 20/00807-5)