Liquid crystalline nanoparticles enable a multifunctional approach for topical psoriasis therapy by co-delivering triptolide and siRNAs

Author(s)

Silvestrini, Ana Vitoria Pupo ; Praca, Fabiola Garcia ; Leite, Marcel Nani ; Fantini, Marcia Carvalho de Abreu ; Frade, Marco Andrey Cipriani ; Bentley, Maria Vitoria Lopes Badra

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 640, p. 17-pg., 2023-05-13.

Abstract

Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-alpha and IL6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolinmediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF alpha, IL-6, IL-113 and TGF-131 levels in LPS-stimulated macrophages. These results support the hypothesis that the codelivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy. (AU)

• FAPESP's process: 18/08253-9 - Development and characterization of liquid-crystal phase nanodispersion as a multifunctional carrier system of TNF-alpha siRNA and Triptolide in the topical treatment of psoriasis
• Grantee: Ana Vitória Pupo Silvestrini
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants