NANO-IN-NANO MULTIFUNCTIONAL POLYMERIC SYSTEMS FOR COLON-SPECIFIC RELEASE OF CAMPTOTHECIN WITH POTENTIAL APPLICATION IN THE TREATMENT OF COLORECTAL CANCER

• Grant number: 24/23066-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Lucas Henrique Domingos da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Colorectal Cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with high incidence rates and a significant impact on public health. Despite advancements in conventional therapies, such as surgery, chemotherapy, and radiotherapy, many patients face challenges related to treatment resistance, severe side effects, and disease recurrence. CRC treatment typically involves surgical intervention, with radiotherapy and chemotherapy being employed in advanced cases. However, these approaches often result in severe adverse effects for patients. Camptothecin (CPT), an alkaloid with antitumor activity, works by inhibiting topoisomerase I, an enzyme found in high concentrations in tumors. This mechanism makes CPT a promising alternative for tumor treatment. Oral administration offers a convenient and patient-friendly approach, particularly for chronic patients undergoing long-term treatment. Its ease of use, painlessness, and potential for self-administration significantly enhance patient quality of life and treatment adherence. The development of drug delivery systems specifically targeting the colon enables a more selective pharmacological action at the tumor site, enhancing therapeutic efficacy while reducing systemic toxicity. A promising technological platform for oral colorectal cancer treatment involves the integration of CPT into polymeric micelles encapsulated in nanoparticles using a nano-in-nano system. This study aims to evaluate the biological potential of polymeric micelles containing camptothecin encapsulated in PLGA-based gastroresistant nanocapsules for colorectal cancer treatment, through both in vivo and in vitro experiments. The systems will be characterized in terms of encapsulation efficiency, morphology, size, zeta potential, and chemical properties. The performance of the system will be assessed via in vitro release studies, cytotoxicity assays in 2D and 3D monoculture models, and an in vivo aberrant crypt foci assay to evaluate the platform's effectiveness against pre-neoplastic lesions in rat colons. (AU)