Liquid crystalline phase nanodispersions enable skin delivery of siRNA

Author(s)

Moura de Carvalho Vicentini, Fabiana Testa ^[1] ; Depieri, Livia Vieira ^[1] ; Morseli Polizello, Ana Cristina ^[1] ; Del Ciampo, Jose Orestes ^[1] ; Cropanese Spadaro, Augusto Cesar ^[1] ; Fantini, Marcia C. A. ^[2] ; Lopes Badra Bentley, Maria Vitoria ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS; v. 83, n. 1, p. 16-24, JAN 2013.
• Web of Science Citations: 34

Abstract

The ability of small interfering RNAs (siRNAs) to potently but reversibly silence genes in vivo has made them particularly well suited as a new class of drugs that interfere with disease-causing or disease-promoting genes. However, the largest remaining hurdle for the widespread use of this technology in skin is the lack of an effective delivery system. The aim of the present study was to evaluate nanodispersed systems in liquid crystalline phases that deliver siRNA into the skin. The proposed systems present important properties for the delivery of macromolecules in a biological medium, as they are formed by substances that have absorption-enhancing and fusogenic effects; additionally, they facilitate entrapment by cellular membranes due to their nano-scale structure. The cationic polymer polyethylenimine (PEI) or the cationic lipid oleylamine (OAM) were added to monoolein (MO)-based systems in different concentrations, and after dispersion in aqueous medium, liquid crystalline phase nanodispersions were obtained and characterized by their physicochemical properties. Then, in vitro penetration studies using diffusion cell and pig ear skin were carried out to evaluate the effect of the nanodispersions on the skin penetration of siRNA; based on these results, the nanodispersions containing MO/OA/PEI/aqueous phase (8:2:5:85, w/w/w/w) and MO/OA/OAM/aqueous phase (8:2:2:88, w/w/w/w) were selected. These systems were investigated in vivo for skin penetration, skin irritation, and the ability to knockdown glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein levels in animal models. The results showed that the studied nanodispersions may represent a promising new non-viral vehicle and can be considered highly advantageous in the treatment of skin disorders; they were effective in optimizing the skin penetration of siRNA and reducing the levels of the model protein GAPDH without causing skin irritation. (c) 2012 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 09/00332-8 - Development of liquid crystal nanodispersions for skin delivery of small interfering RNAs: in vitro and in vivo cutaneous penetration studies
• Grantee: Fabiana Testa Moura de Carvalho Vicentini
• Support Opportunities: Scholarships in Brazil - Post-Doctoral