巯基化壳聚糖：各种巯基配体对渗透增强和 P-糖蛋白抑制性质的影响。
Thiolated chitosans: influence of various sulfhydryl ligands on permeation-enhancing and P-gp inhibitory properties.
机构信息
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
出版信息
Drug Dev Ind Pharm. 2011 Jun;37(6):648-55. doi: 10.3109/03639045.2010.534484. Epub 2011 Jan 11.
PURPOSE
The influence of various sulfhydryl ligands on permeation-enhancing and P-glycoprotein (P-gp) inhibitory properties of the six established thiolated chitosan conjugates was investigated using Rhodamine-123 (Rho-123) and fluorescein isothiocyanate-dextran 4 (FD4) as model compounds.
METHODS
Permeation of these compounds was tested on freshly excised rat intestine in Ussing-type chambers. Apparent permeability coefficients (Papp) were calculated and compared to values obtained from the buffer only control.
RESULTS
The lyophilized polymers had a thiol group content in the range of 230-520 μmol/g. Results of this study led to the following rank order in permeation enhancement: chitosan-6-mercaptonicotinic acid (chitosan-6MNA) > chitosan-cysteine (chitosan-Cys) > chitosan-glutathione (chitosan-GSH) > chitosan-4-thiobutylamidine (chitosan-TBA) > chitosan-thioglycolic acid (chitosan-TGA) > chitosan-N-acetyl cysteine (chitosan-NAC). In P-gp inhibition studies, 0.5% (m/v) chitosan-NAC showed the highest inhibitory effect on P-gp, where the Papp was determined to be 3.78-fold increased compared with the buffer control. Among these thiolated chitosans, chitosan-NAC and chitosan-6MNA are the most effective polymers being responsible for P-gp inhibition and permeation enhancement, respectively.
CONCLUSION
These thiolated chitosans would therefore be advantageous tools for enhancing the noninvasive bioavailability of active pharmaceutical ingredients.
目的
研究了不同巯基配体对 6 种已合成的巯基化壳聚糖缀合物的渗透增强和 P 糖蛋白（P-gp）抑制特性的影响，以罗丹明 123（Rho-123）和荧光素异硫氰酸酯-葡聚糖 4（FD4）为模型化合物。
方法
在 Ussing 型室中用新鲜离体大鼠肠对这些化合物的渗透进行测试。计算表观渗透系数（Papp）并与仅缓冲对照值进行比较。
结果
冻干聚合物的巯基含量在 230-520 μmol/g 范围内。本研究的结果导致以下渗透增强的排序：壳聚糖-6-巯基烟酸（壳聚糖-6MNA）>壳聚糖-半胱氨酸（壳聚糖-Cys）>壳聚糖-谷胱甘肽（壳聚糖-GSH）>壳聚糖-4-巯基丁脒（壳聚糖-TBA）>壳聚糖-巯基乙酸（壳聚糖-TGA）>壳聚糖-N-乙酰半胱氨酸（壳聚糖-NAC）。在 P-gp 抑制研究中，0.5%（m/v）壳聚糖-NAC 对 P-gp 的抑制作用最高，与缓冲对照相比，Papp 增加了 3.78 倍。在这些巯基化壳聚糖中，壳聚糖-NAC 和壳聚糖-6MNA 是最有效的聚合物，分别负责 P-gp 抑制和渗透增强。
结论
因此，这些巯基化壳聚糖将是增强活性药物成分非侵入性生物利用度的有利工具。
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