Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure-activity relationships, molecular dynamics and dermal delivery

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Raquel S Teixeira (Author) Other; Tania F G G Cova (Author) Other; Sergio M C Silva (Author) Other; Rita Oliveira (Author) Other; Luisa L C do Vale (Author) FCUP; Eduardo F Marques (Author) FCUP; Alberto A C C Pais (Author) Other; Francisco J B Veiga (Author) Other

Journal

Title: European Journal of Pharmaceutics and Biopharmaceutics

Vol. 93

Pages: 205-213

ISSN: 0939-6411

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 16 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00A-CW1

DOI: 10.1016/j.ejpb.2015.02.024

Abstract (EN): This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations. (C) 2015 Published by Elsevier B.V.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9