Evaluation of biocompatibility and antitumor activity of liposome-loaded into retrograde starch and pectin microparticles in triple co-culture spheroid model for colorectal cancer

• Grant number: 24/17888-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 25, 2025
• End date: March 24, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Aline Martins dos Santos
• Supervisor: Bruno Filipe Carmelino Cardoso Sarmento
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Universidade do Porto (UP), Portugal
• Associated to the scholarship: 20/06093-4 - Multifunctional systems based on liposomes carried into retrograded starch and pectin microparticles for colon-specific release of 5-fluorouracil in the treatment of Colorectal Cancer, BP.PD

Abstract

Colorectal cancer (CRC) is the third highest worldwide incidence and the fourth leading cause of cancer-related mortality, highlighting the need of new therapeutic alternatives for the treatment of this pathology. 5-fluorouracil (5-FU) still represents one of the most effective chemotherapy drugs used in standard and combined CRC therapy, however, limitations associated with short half-life and off-target toxicity effects, limit its therapeutic efficacy. The use of combinatorial strategies, such as 5-FU-loaded liposomes incorporated into retrograded starch and pectin microparticles (nano-in-microparticle systems) for colon-targeted delivery represent potential tools for CRC therapy by increasing drug concentration at the tumor site. This is because the retrograded starch (RS) escapes digestion in the upper portions of the gastrointestinal tract (GIT) and is digested only in the colon. Its association with pectin was attributed to the optimization of the retrogradation process, increasing the RS yield, presenting advantageous properties for obtaining colonic delivery systems. However, the clinical translation of nano-in-microparticle systems for the treatment of CRC is limited by the lack of models capable of providing reliable and predictive therapeutic results on their in vivo efficiency. Multicellular 3D models have been widely used in preclinical research for the development of drug delivery systems, by mimicking the main genetic, physical and mechanical characteristics of the tumor microenvironment. In this context, this research project aims to evaluate the biocompatibility and antitumor activity of liposome-loaded into retrograded starch and pectin microparticles in colorectal cancer triple co-culture spheroid model, to be held at the Institute for Research and Innovation in Health of the University of Porto, under supervision of Professor Bruno Filipe Carmelino Cardoso Sarmento. This study will contribute decisively to the understanding of the effectiveness of the proposed new systems for colonic oral drug delivery for CRC therapy.