Development and evaluation of topical nanoscaffolds enriched with lipid nanoparticles for the co-delivery of an H2S donor and an anti-inflammatory peptide and treatment of skin inflammatory conditions

• Grant number: 24/18312-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Julia Sapienza Passos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors, AP.JP2

Abstract

Psoriasis is a chronic inflammatory skin disease that presents diverse clinical manifestations and significantly impacts the quality of life of patients. Current treatments, particularly the first-line treatment with topical corticosteroids, often cause several adverse effects both locally and systemically, highlighting the need for effective and safe novel strategies for the long-term management of the disease. In this project, we propose an innovative nanotechnology-based delivery system for psoriasis treatment, based on the co-delivery of a slow hydrogen sulfide (H2S) donor, GYY4137, and a cell-penetrating peptide (CPP) with anti-inflammatory properties, YARA. The system is based on the incorporation of nanostructured lipid carriers (NLC) in crosslinked chitosan-hyaluronic acid hydrogels. The NLCs will be optimized to increase the stability of GYY, protect it from premature release and increase its skin penetration, while the hydrogel will be developed to increase the skin retention time and sustain the release of the active compounds. The aims of this project are: (i) to develop and characterize NLCs containing GYY4137 using dynamic light scattering techniques, electron microscopy and evaluation of the encapsulation, stability and release of the GYY donor; (ii) to incorporate the NLCs into the hydrogel that also entraps the YARA peptide by electrostatic interactions; (iii) to evaluate the system's ability to promote the skin localization of the actives; (iv) to evaluate the cellular effects in vitro and determine the efficacy and safety of the system in a murine model of psoriasis in vivo. The experimental strategy proposed here will lead to the development of an innovative nanotechnology-based system that can potentially offer new advantages and advance the treatment of psoriasis. (AU)