In vitro permeation of a pegylated naltrexone prodrug across microneedle-treated skin.
In vitro permeation of a pegylated naltrexone prodrug across microneedle-treated skin.
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DOI：
10.1016/j.jconrel.2010.05.034
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发表时间：
2010-08-17
期刊：
影响因子：
--
通讯作者：
Stinchcomb AL
中科院分区：
文献类型：
--
作者：
Milewski M;Yerramreddy TR;Ghosh P;Crooks PA;Stinchcomb AL
微针 (MN) 是增加皮肤对异生素的渗透性的有用工具。先前的研究表明，仅使用 MN 皮肤预处理即可显着改善盐酸纳曲酮 (NTX) 的经皮通量；然而，为了获得更好的治疗效果，还需要进一步增强。这项体外研究的目标是将微针皮肤预处理与高水溶性聚乙二醇化纳曲酮前药（聚乙二醇-NTX，PEG-NTX）的使用相结合，以研究其在不同浓度下的透皮转运。研究了前药的溶解度和稳定性。使用 MN 处理的小型猪皮肤进行体外扩散实验来评估聚乙二醇化前药的性能。结果表明，与理想行为有很大偏差，通过 MN 处理的皮肤的通量与供体溶液中的前药浓度呈非线性关系。虽然在测试的较低浓度范围内，前药通量增加与浓度增加成正比，但在高浓度下，它没有表现出这种依赖性。正如斯托克斯-爱因斯坦方程所预测的那样，考虑到有效前药扩散率随着粘度的增加而降低，为观察到的通量值提供了理论依据。假设增加供体溶液的粘度可为聚乙二醇化 NTX 前药提供曲线渗透曲线。
Microneedles (MN) are a useful tool for increasing skin permeability to xenobiotics. Previous research showed marked improvement in the percutaneous flux of naltrexone (NTX) hydrochloride by the use of MN skin pretreatment alone; however, for better therapeutic effect, further enhancement is desired. The goal of this in vitro study was to combine microneedle skin pretreatment with the use of a highly water-soluble PEGylated naltrexone prodrug (polyethyleneglycol-NTX, PEG-NTX) to investigate its transdermal transport at varying concentrations. Solubility and stability of the prodrug were investigated. In vitro diffusion experiments employing MN-treated minipig skin were used to evaluate the performance of the PEGylated prodrug. The results revealed substantial deviation from ideal behavior, with the flux through MN-treated skin having a nonlinear relationship to the prodrug concentration in the donor solution. While in the lower concentration range tested the prodrug flux increase was proportional to the concentration increase, at high concentrations it showed no such dependence. Accounting for the decrease in the effective prodrug diffusivity accompanying the increase in viscosity, as predicted by the Stokes-Einstein equation, provided a rationale for the observed flux values. Increasing the viscosity of the donor solution is hypothesized to afford a curvilinear permeation profile for the PEGylated NTX prodrug.
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影响因子：
4.7
作者：
Basu, Amartya;Yang, Karen;Filpula, David
通讯作者：
Filpula, David
影响因子：
3
作者：
GENDIMENICO, GJ;LIEBEL, FT;MEZICK, JA
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MEZICK, JA
影响因子：
2.2
作者：
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通讯作者：
Maillard, JY
DOI：
10.1111/j.1365-2885.2007.00879.x
发表时间：
2007-10-01
影响因子：
1.3
作者：
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通讯作者：
Mills, P. C.
影响因子：
5.8
作者：
Kretsos, Kosmas;Miller, Matthew A.;Kasting, Gerald B.
通讯作者：
Kasting, Gerald B.