Development and in vitro biological evaluation of colon-specific polymeric nanoparticles for the co-encapsulation of camptothecin and butyrate as a potential strategy for the treatment of colorectal cancer

• Grant number: 25/00769-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: December 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Rita Cristina Gonçalves de Melo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Worldwide, colorectal cancer (CRC) is one of the leading causes of cancer-related deaths, with high incidence rates. The conventional treatment for CRC is intravenous chemotherapy, which typically presents limited bioavailability, nonspecific biodistribution, adverse effects, and therapeutic resistance by patients. Camptothecin (CPT) is an alkaloid with known antineoplastic action on CRC; however, its limitations, such as low aqueous solubility, instability in the physiological environment, and low permeability, hinder its clinical use. Poly(lactic-co-glycolic acid) (PLGA) is a polymer widely used in the preparation of nanoparticles because it is biocompatible and ensures drug bioavailability. However, PLGA nanoparticles have a negative surface charge, which hinders cellular internalization. Chitosan (CS), a cationic polymer, can be used to coat PLGA nanoparticles and improve their characteristics, increasing permeability and providing mucoadhesiveness. Butyrate, a short-chain fatty acid, is a postbiotic that presents antioxidant, anti-inflammatory, antiproliferative and antineoplastic activities. Thus, when associated with CPT, it can exert synergistic or secondary effects that improve the efficacy of pharmacotherapy. In this context, the development of innovative systems for drug delivery, such as polymeric nanoparticles, emerges as a promising alternative to improve the limitations presented by these drugs. The objective of the present work is to develop nanoparticles Polymeric nanoparticles based on PLGA and chitosan for the co-encapsulation of CPT and butyrate, aiming at the treatment of colorectal cancer. The nanoparticles will be developed and characterized regarding size, morphology, zeta potential, polydispersity index, concentration and encapsulation efficiency. The in vitro release will be evaluated under conditions that simulate the variations of the gastrointestinal tract. In addition, tests will be performed to evaluate cell viability in 2D and 3D models and antiangiogenic activity in an egg chorioallantoic membrane model. It is expected to obtain a system that can present potential application in the conventional treatment of CRC.