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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

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

Revista

Título: AAPS Journal

Vol. 15

Páginas: 1119-1127

ISSN: 1550-7416

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 15 Citações

Scopus - 17 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

CORDIS: Ciências Físicas > Química > Química física > Química das superfícies ; Ciências da Saúde > Ciências farmacológicas > Farmácia ; Ciências Físicas > Química > Bioquímica

Projetos Associados

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

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica