Impact of Iontophoresis on the Ocular Biodistribution of Polymeric Nanoparticles Conjugated with Hyaluronic Acid

• Grant number: 24/16717-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Renata Fonseca Vianna Lopez
• Grantee: Izabella Cristina Bernardo Maríngolo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 22/03521-0 - Investigation of physical methods associated with drug delivery systems in the local immune and antimicrobial response, AP.TEM

Abstract

The growing interest in ocular drug delivery systems is driven by the advantages of nanoparticles in drug administration, including sustained release and reduced side effects. Hyaluronic acid (HA) is promising both for the fabrication of nanoparticles due to its biocompatibility and bioadhesion properties and for imparting therapeutic properties by interacting with CD44 receptors in ocular structures, which are crucial for cell adhesion and signaling. However, effective intraocular nanoparticle delivery is challenging due to their size, which limits their permeation into ocular tissues. Iontophoresis, an electrically-based technique, can enhance the transport of these particles and target them to specific areas of the eye, as well as potentially alter the biomechanical properties of the cornea. This latter can benefit the treatment of keratoconus. This project aims to investigate the impact of combining polymeric nanoparticles conjugated with HA and iontophoresis on the cornea's ocular distribution, immune response, and biomechanical properties. Fluorescent polyacrylic acid nanoparticles conjugated with HA and labeled with rhodamine will be prepared and characterized through emulsion polymerization using a redox radical method. The spherical nanoparticles obtained will be mechanically elongated to evaluate the ocular distribution of nanoparticles in different shapes, spherical and elongated. The ocular distribution and immune response of the nanoparticles will be studied in vivo in rabbits after topical application, and the effect of iontophoresis will be investigated regarding its influence on nanoparticle distribution, immune response, and the biomechanical properties of the cornea. The research results can provide new strategies for more effective and less invasive ocular treatments, contributing to developing innovative formulations and therapeutic approaches.