Evaluation of chondroitin sulfate/hyaluronic acid blended hydrogels as a novel subcutaneous drug and peptide delivery system

• Grant number: 25/04793-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 05, 2025
• End date: September 04, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Isabella Draszesski Malagó
• Supervisor: Alyssa Panitch
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Georgia Institute of Technology, United States
• Associated to the scholarship: 22/00997-4 - Nanostructured lipid carriers for co-encapsulation and sustained release of fenretinide and perillyl alcohol in the mammary tissue aiming at prevention of development and recurrences of Breast Cancer, BP.DD

Abstract

In this project, we propose to develop and evaluate an in situ-forming multifunctional hydrogel for intramammary delivery of fenretinide and a mitogen-activated protein kinase-activated protein kinase-2 inhibitor peptide (YARA) aiming at breast cancer chemoprevention. Due to the low aqueous solubility of fenretinide, we envisioned hydrogels enriched with fenretinide-loaded nanostructured lipid carriers (NLCs). Hydrogels will be produced with chondroitin sulfate/hyaluronic acid (CS/HA) blends. In the first part of this project, we will define suitable CS/HA ratios, characterize the structure of selected hydrogels, and evaluate the in vitro release of the compounds and their cytotoxicity to cancer cells. In the second part, ex vivo studies will be performed using commercially available skin explants as a model for the subcutaneous (SC) tissue. Hydrogel structural organization and local retention, release and diffusion of incorporated compounds will be assessed by quantifying fenretinide and YARA in the culture medium and explants. The cellular effects of selected hydrogels will be assessed on breast cells viability, proliferation and cell cycle using MCF-7, T-47D and MDA-MB-231 breast cancer cells. To evaluate the selectivity of drug-loaded hydrogels, MCF-10A nontumoral breast cells will be employed. The irritative potential and inflammatory reactions mediated by hydrogel injection will be evaluated through quantification of secreted cytokines and histological analysis of the tissue. Finally, we propose to assess the applicability of skin explants to generate an ex vivo breast cancer model through the injection of MDA-MB-231 cells in the SC tissue and assess the efficacy of the hydrogel to prevent tumor development.