Colon-specific systems based on polymeric nanoparticles carried within protein microparticles for camptothecin delivery in colorectal cancer treatment

• Grant number: 24/23244-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: December 31, 2029
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Felipe Tita de Lima
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Cancer is a group of diseases characterized by genetic mutations in cells, leading to the uncontrolled growth of abnormal cells. Among the most common types, colorectal cancer (CRC) ranks third in global cancer-related deaths and is one of the five most diagnosed cancers worldwide. The conventional treatment for CRC is intravenous therapy; however, the lack of drug specificity can result in significant toxicities. Camptothecin (CPT), an antineoplastic agent derived from the plant Camptotheca acuminata, is used in CRC treatment, acting during the S phase of the cell cycle and inhibiting the TOP-1 enzyme. However, its low water solubility and instability at physiological pH limit its efficacy. Therefore, colon-specific delivery of CPT using polymeric nanoparticles to improve therapeutic efficacy and increase the stability of active compounds has been explored in the literature through the development of oral delivery systems. Combining strategies such as developing mucoadhesive nanoparticles and incorporating them into microparticles to protect the system against the variable conditions of the gastrointestinal tract (GIT) represents a promising platform for colon-specific CPT delivery. The bio/mucoadhesive properties of ¿-carrageenan make it a highly promising polymer for developing nanoparticles, while the use of natural polymers resistant to enzymatic digestion and acidic pH in the upper GIT, such as zein, is an effective strategy for developing microparticles for colon-specific delivery. Thus, the present study proposes the development of a multifunctional system based on microparticles containing polymeric nanoparticles for the oral administration of CPT in CRC treatment. Optimized conditions for system development will be determined, and the system will be characterized from a physicochemical perspective. Additionally, the biological performance of these systems will be evaluated through in vitro release studies, cytotoxicity assessments in 2D and 3D cell culture models, and anti-angiogenic activity evaluation using the chorioallantoic membrane (CAM) assay in chicken eggs (ex vivo).