Molecular Inclusion Complexes of β-Cyclodextrin Derivatives Enhance Aqueous Solubility and Cellular Internalization of Paclitaxel: Preformulation and In vitro Assessments.
Molecular Inclusion Complexes of β-Cyclodextrin Derivatives Enhance Aqueous Solubility and Cellular Internalization of Paclitaxel: Preformulation and In vitro Assessments.
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DOI：
10.13188/2327-204x.1000011
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发表时间：
2015-01-10
期刊：
影响因子：
--
通讯作者：
Minko T
中科院分区：
文献类型：
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作者：
Shah M;Shah V;Ghosh A;Zhang Z;Minko T
低水溶解度和渗透性的药物在设计有效和安全的制剂方面面临着巨大的挑战。在一个简单的处方中，协同的溶解性和渗透性增强可以提高此类药物的生物利用度和疗效。为了克服紫杉醇®临床配方的局限性，紫杉醇(PTX)被重新配制成适合于非肠外给药的各种β-环糊精(CD)衍生物。结果表明，β-CDS可以在较低的摩尔比下有效地与PTX形成络合物，使其在水中的溶解度提高约500倍，并改善了PTX的细胞内化作用。所有β-CD衍生物都被发现是安全的赋形剂，因为没有一种表现出可检测到的细胞遗传毒性迹象。结果表明，CD-PTX络合物显著提高了药物的细胞毒性。研究得出结论，CD-PTX制剂可以取代目前静脉滴注的PTX，从而避免使用非惰性赋形剂乳膏EL。
Drugs with low aqueous solubility and permeability possess substantial challenges in designing effective and safe formulations. Synergistic solubility and permeability enhancement in a simple formulation can increase bioavailability and efficacy of such drugs. To overcome limitations of the clinical formulation of Taxol®, Paclitaxel (PTX) was reformulated with various β-cyclodextrin (CD) derivatives suitable for parenteral administration. Results indicated that β-CDs can efficiently form complexes with PTX at lower molar ratios, enhance aqueous solubility up to 500 times and improved cellular internalization of PTX. All β-CD derivatives were found to be safe as excipient since none showed detectable signs of cyto-genotoxicity. As a result, the CD-PTX complexes significantly increased the cytotoxicity of the drug. The study concluded that CD-PTX formulations could substitute the current intravenous infusion of PTX obviating the use of non-inert excipient Cremophor EL.