Investigation of substituted 6-aminohexanoates as skin penetration enhancers

Brychtova, Katerina; Dvořáková, Lenka; Opatřilová, Radka; Raich, Ivan; Kacerova, Sandra; Plaček, Lukáš; Kalinowski, Danuta S.; Richardson, Des R.; Jampílek, Josef

doi:10.1016/j.bmc.2011.11.033

Cited by 6 publications

(2 citation statements)

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“…The protective nature of the SC is attributed to its multilayered wall-like structure, in which terminally differentiated keratinocytes are embedded in an intercellular lipid-rich matrix. Various approaches have been developed in recent decades to overcome the skin barrier properties including physical approaches using iontophoresis, sonophoresis and microneedles [3,4], chemical approaches using penetration enhancers, and biochemical approaches using liposomal vesicles and enzyme inhibition [5,6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

“…Among various skin permeating agents, the heterocyclic compounds such as azone and 6-amino hexanoates, are well-studied chemical penetration enhancers, which contain lipid alkyl chains and large polar head groups that have been determined to be vital for their respective activities [6,9]. This class of permeation enhancers has been shown to increase skin permeability by disordering or ‘fluidizing’ the lipid structure of the stratum corneum and forming micro cavities within the lipid bilayers, which ultimately increase the diffusion coefficient of a drug.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis of Novel Lipids as Chemical Permeation Enhancers and Development of Nanoparticle System for Transdermal Drug Delivery

et al. 2013

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In the present study, we designed and developed novel lipids that include (Z)-1-(Octadec-9-en-1-yl)-pyrrolidine (Cy5T), 1, 1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium iodide (Cy5), (Z)-1-(Octadec-9-en-1-yl)-piperidine (Cy6T), and 1, 1-Di-((Z)-octadec-9-en-1-yl) piperidin-1-ium iodide (Cy6) to enhance the transdermal permeation of some selected drugs. Firstly, we evaluated the transdermal permeation efficacies of these lipids as chemical permeation enhancers in vehicle formulations for melatonin, ß-estradiol, caffeine, α-MSH, and spantide using franz diffusion cells. Among them Cy5 lipid was determined to be the most efficient by increasing the transdermal permeation of melatonin, ß-estradiol, caffeine, α-MSH, and spantide by 1.5 to 3.26-fold more at the epidermal layer and 1.3 to 2.5-fold more at the dermal layer, in comparison to either NMP or OA. Hence we developed a nanoparticle system (cy5 lipid ethanol drug nanoparticles) to evaluate any further improvement in the drug penetration. Cy5 lipid formed uniformly sized nanoparticles ranging from 150–200 nm depending on the type of drug. Further, Cy5 based nanoparticle system significantly (p<0.05) increased the permeation of all the drugs in comparison to the lipid solution and standard permeation enhancers. There were about 1.54 to 22-fold more of drug retained in the dermis for the Cy5 based nanoparticles compared to OA/NMP standard enhancers and 3.87 to 66.67-fold more than lipid solution. In addition, epifluorescent microscopic analysis in rhodamine-PE permeation studies confirmed the superior permeation enhancement of LEDs (detection of fluorescence up to skin depth of 340 μm) more than lipid solution, which revealed fluorescence up to skin depth of only 260 μm. In summary the present findings demonstrate that i) cationic lipid with 5 membered amine heterocyclic ring has higher permeating efficacy than the 6 membered amine hertocyclic ring. ii) The nanoparticle system prepared with Cy5 showed significant (p<0.05) increase in the permeation of the drugs than the control penetration enhancers, oleic acid and NMP.

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