Structure Activity Relationships in Alkylammonium C12-Gemini Surfactants Used as Dermal Permeation Enhancers
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 4
Abstract
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 μg 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 μg 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.
Authors and Affiliations
Sérgio M. C. Silva, João J. S. Sousa, Eduardo F. Marques, Alberto A. C. C. Pais, Bozena B. Michniak-Kohn
Keywords
Related Articles
- EP ID EP681171
- DOI 10.1208/s12248-013-9518-y
- Views 91
- Downloads 0
Particle size analysis of concentrated phospholipid microemulsions: II. Photon correlation spectroscopy
The solvated droplet size of concentrated water-in-oil (w/o) microemulsions prepared frome egg and soy lecithin/water/isopropyl myristate and containing short-chain alcohol cosurfactants has been determined using photon...
Corrigendum: 2007 highlights of advances in the pharmaceutical sciences: An American Association of Pharmaceutical Scientists (AAPS) perspective
A Qualitative and Quantitative Proteomic Study of Human Microdialysate and the Cutaneous Response to Injury
The online version of this article (doi:10.1208/s12248-011-9269-6) contains supplementary material, which is available to authorized users.
GATG Dendrimers and PEGylated Block Copolymers: from Synthesis to Bioapplications
Dendrimers are synthetic macromolecules composed of repetitive layers of branching units that emerge from a central core. They are characterized by a tunable size and precise number of peripheral groups which determine t...
Optimization of the Antitumor Activity of Sequence-specific Pyrrolobenzodiazepine Derivatives Based on their Affinity for ABC Transporters
The online version of this article (doi:10.1208/s12248-010-9225-x) contains supplementary material, which is available to authorized users.