Penetratin-induced transdermal delivery from H_II mesophases of sodium diclofenac

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• 作者：Marganit Cohen-Avrahami¹ ; Dima Libster ; Abraham Aserin ; Nissim Garti ; ^{garti@vms.huji.ac.il}
• 关键词：Hexagonal liquid crystals ; Cell penetrating peptides ; Transdermal delivery systems ; SD-NMR ; Skin FTIR spectroscopy ; Penetratin
• 刊名：Journal of Controlled Release
• 出版年：2012
• 出版时间：10 May, 2012
• 年：2012
• 卷：159
• 期：3
• 页码：419-428
• 全文大小：1053 K

文摘

Penetratin, a cell penetrating peptide is embedded within a reversed hexagonal (H_II) mesophase for improved transdermal delivery of sodium diclofenac (Na-DFC). The H_II mesophase serves as the solubilization reservoir and gel matrix whereas penetratin is the transdermal penetration enhancer for the drug. The systems were characterized and the interactions between the components were determined by SAXS, ATR-FTIR and SD-NMR. High affinity of Na-DFC to glycerol monooleate (GMO) was revealed, associated with increasing the order within the water channels. This affinity is enhanced upon heating and seems to be associated with GMO dehydration. Penetratin (PEN) is entrapped at the hydrophilic region of the H_II mesophase, between the GMO headgroups, reducing the order of the system and decreasing the size of the hexagonal domains.

The transdermal delivery rate of Na-DFC through porcine skin, from the H_II mesophases, was enhanced by PEN and so also the cumulative transport crossing the skin. PEN induced accelerated drug diffusion through the stratum corneum, towards the different skin layers.

The transdermal delivery enhancement is explained from the results of the ATR-FTIR analysis. It seems that PEN accelerates the structural transition of skin lipids from hexagonal to liquid. The disordering results in enhanced diffusion of Na-DFC through the stratum corneum, followed by enhanced overall penetration of the drug.