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环吡酮从基于羟丙基壳聚糖的水溶性指甲油中的体外经甲渗透

In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer.

作者信息

Monti Daniela, Saccomani L, Chetoni P, Burgalassi S, Saettone M F, Mailland F

机构信息

Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Pisa, Italy.

出版信息

Drug Dev Ind Pharm. 2005 Jan;31(1):11-7. doi: 10.1081/ddc-43935.

Abstract

Commercial antimycotic nail lacquers are commonly based on water-insoluble resins. The present study was aimed at evaluating a novel, experimental nail lacquer (P-3051, Polichem SA, Lugano, Switzerland) based on the water-soluble film-forming agent hydroxypropyl chitosan (HPCH). The in vitro permeation of ciclopirox (CPX) from P-3051 and from a commercial, water-insoluble lacquer based on a vinyl resin (Penlac, Aventis Pharma), was investigated using thin membranes obtained from bovine hooves, an accepted model for human nails. Similar CPX permeation fluxes at steady state through the membranes, but significantly different lag times were observed for P-3051 and Penlac, when these were tested as dry films. The formulations thus appeared to influence only the time required by CPX to saturate the membrane, and not the final drug concentration gradient in the membrane. Permeation experiments performed on the same membranes and on hairless mouse skin with P-3051 and with a similar, HPCH-free vehicle (ERV), both tested in liquid form, disproved the possibility that HPCH might act as a permeation enhancer for CPX in either substrate. The possible reasons for the greater efficiency of the HPCH vehicle in terms of CPX transfer from the vehicle itself to the keratin membrane are discussed. This effect might be tentatively attributed to a particular affinity of HPCH for the membrane, resulting in intimate contact and strong adhesion of the HPCH lacquer to the keratin substrate.

摘要

市售抗真菌指甲油通常以水不溶性树脂为基础。本研究旨在评估一种基于水溶性成膜剂羟丙基壳聚糖(HPCH)的新型实验性指甲油(P - 3051,Polichem SA,卢加诺,瑞士)。使用从牛蹄获得的薄膜(一种公认的人类指甲模型),研究了环吡酮(CPX)从P - 3051以及从一种基于乙烯基树脂的市售水不溶性指甲油(Penlac,安万特制药公司)中的体外渗透情况。当将P - 3051和Penlac作为干膜进行测试时,观察到它们在稳态下通过薄膜的CPX渗透通量相似,但滞后时间显著不同。因此,这些制剂似乎仅影响CPX使薄膜饱和所需的时间,而不影响薄膜中最终的药物浓度梯度。在相同的薄膜以及无毛小鼠皮肤上,以液体形式测试了P - 3051和一种类似的不含HPCH的载体(ERV),渗透实验证明HPCH不可能在任何一种基质中作为CPX的渗透促进剂。讨论了HPCH载体在CPX从载体本身转移到角蛋白膜方面效率更高的可能原因。这种效应可能暂时归因于HPCH与膜的特殊亲和力,导致HPCH指甲油与角蛋白基质紧密接触并强烈粘附。

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