Structure Activity Relationships in Alkylammonium C-12-Gemini Surfactants Used as Dermal Permeation Enhancers

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Sergio M C Silva (Author) Other; Joao J S Sousa (Author) Other; Eduardo F Marques (Author) FCUP; Alberto A C C Pais (Author) Other; Bozena B Michniak Kohn (Author) Other

Journal

Title: AAPS Journal

Vol. 15

Pages: 1119-1127

ISSN: 1550-7416

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 17 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Physical sciences > Chemistry > Physical chemistry > Surface chemistry ; Health sciences > Pharmacological sciences > Pharmacy ; Physical sciences > Chemistry > Biochemistry

Associated Projects

115212_2009 - Uma nova abordagem à veiculação de fármacos: lipossomas cataniónicos e nanotubos baseados em derivados de aminoácidos

Other information

Authenticus ID: P-006-6SA

DOI: 10.1208/s12248-013-9518-y

Abstract (EN): The purpose of this study was to determine the ability and the safety of a series of alkylammonium C12-gemini surfactants to act as permeation enhancers for three model drugs, namely lidocaine HCl, caffeine, and ketoprofen. In vitro permeation studies across dermatomed porcine skin were performed over 24 h, after pretreating the skin for 1 h with an enhancer solution 0.16 M dissolved in propylene glycol. The highest enhancement ratio (enhancement ratio (ER) = 5.1) was obtained using G12-6-12, resulting in a cumulative amount of permeated lidocaine HCl of 156.5 mu g cm(-2). The studies with caffeine and ketoprofen revealed that the most effective gemini surfactant was the one with the shorter spacer, G12-2-12. The use of the latter resulted in an ER of 2.4 and 2.2 in the passive permeation of caffeine and ketoprofen, respectively. However, Azone was found to be the most effective permeation enhancer for ketoprofen, attaining a total of 138.4 mu g cm(-2) permeated, 2.7-fold over controls. This work demonstrates that gemini surfactants are effective in terms of increasing the permeation of drugs, especially in the case of hydrophilic ionized compounds, that do not easily cross the stratum corneum. Skin integrity evaluation studies did not indicate the existence of relevant changes in the skin structure after the use of the permeation enhancers, while the cytotoxicity studies allowed establishing a relative cytotoxicity profile including this class of compounds, single chain surfactants, and Azone. A dependence of the toxicity to HEK and to HDF cell lines on the spacer length of the various gemini molecules was found.

Language: English

Type (Professor's evaluation): Scientific