Obtaining lyophilized liquid-crystalline nanoparticles (LCNs) for siRNA delivery: prospecting for cryoprotectants, characterization of colloidal properties, stability and in vitro evaluation

• Grant number: 25/05946-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Livia Cirizola Alves Coelho
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

Liquid-crystalline nanoparticles (LCNs) have hybrid properties, combining characteristics of isotropic fluids and crystalline solids, and are emerging as potential carriers of small interfering RNA (siRNA) in antisense gene therapy. The siRNA has stood out for its simple and safe approach, but its instability and susceptibility to degradation corroborate the development of stabilization strategies. This project aims to produce and optimize LCNs by adjusting lipid ratios or introducing new components to improve the stability of the LCN/siRNA lipoplex. To this end, the addition of cryoprotectants will be strategically evaluated to ensure stability during freeze-drying while preserving the structural integrity of the NLCs and siRNA. Analytical tests will be carried out to investigate the physicochemical properties, molecular complexation and stability of the LCNs before and after freeze-drying. In addition, cellular studies, such as cell viability and internalization, will be carried out to assess the interaction of LCNs with cells, followed by the evaluation of siRNA release and permeation into the skin layers. It is hoped that this innovative approach will provide advances in the delivery of nucleic acids, as well as in the processes for obtaining products based on nanotechnology and siRNA, with a view to more stable preparations. (AU)