Multifunctional liquid-crystalline nanoparticles for co-release of siRNAs and piperine in topical treatment of vitiligo: development, characterization and in vitro studies

• Grant number: 22/01969-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2022
• Effective date (End): March 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Ana Vitória Pupo Silvestrini
• 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

Vitiligo is a multifactorial autoimmune disease characterized by hypopigmented macules and patches on the skin and/or mucous membranes, which occur secondary to the destruction of melanocytes. Currently, therapeutic strategies still present unsatisfactory repigmentation rates and high indices of recurrence and side effects. Because of this, the search for new treatments has emerged for the use of therapeutic agents aimed at specific targets of the immunopathological cascade. In this context, we propose the combination of antisense therapy, based on small interfering RNA (siRNA) targeted at specific targets, such as IFN-gama and HSP70, which play a predominant role in the development and progress of the disease. In addition, the combination of the active piperine, an alkaloid derived from Piper nigrum pepper, will contribute to melanogenic effects and control of oxidative stress. Thus, to enable simultaneous cutaneous delivery, therapeutic agents will be carried by liquid-crystalline nanoparticles (LCNs). The LCNs will be produced by top-down and bottom-up (by microfluidic technique - BEPE proposal) approaches, and their colloidal characteristics will be determined by physicochemical techniques, such as dynamic and electrophoretic light scattering, encapsulation efficiency, low-angle X-ray scattering, electrophoretic profile of the siRNA, release kinetics and biological membrane interaction using Franz diffusion cell. Studies at the cellular level will be carried out in different experimental models to investigate cytocompatibility, cellular interaction and anti-inflammatory, antioxidant and melanogenic therapeutic efficacy. The experimental strategy suggested in this project will result in a study of technological and therapeutic feasibility of multifunctional liquid crystals for the topical therapy of vitiligo.