β-环糊精衍生物的分子包合物增强紫杉醇的水溶性和细胞摄取：制剂前研究与评估
Molecular Inclusion Complexes of β-Cyclodextrin Derivatives Enhance Aqueous Solubility and Cellular Internalization of Paclitaxel: Preformulation and Assessments.
作者信息
Shah Milin, Shah Vatsal, Ghosh Anasuya, Zhang Zheng, Minko Tamara
机构信息
Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA ; New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
出版信息
J Pharm Pharmacol (Los Angel). 2015 Jan 10;2(2):8. doi: 10.13188/2327-204X.1000011.
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.
水溶性和渗透性低的药物在设计有效且安全的制剂方面面临重大挑战。在简单制剂中协同提高溶解度和渗透性可增加此类药物的生物利用度和疗效。为克服紫杉醇临床制剂的局限性，用各种适合肠胃外给药的β-环糊精（CD）衍生物对紫杉醇（PTX）进行了重新配方。结果表明，β-环糊精能在较低摩尔比下与PTX有效形成复合物，将水溶性提高多达500倍，并改善PTX的细胞内化。所有β-环糊精衍生物作为辅料均被发现是安全的，因为没有一种显示出可检测到的细胞遗传毒性迹象。因此，CD-PTX复合物显著增加了药物的细胞毒性。该研究得出结论，CD-PTX制剂可替代当前的PTX静脉输注，避免使用非惰性辅料聚氧乙烯蓖麻油（Cremophor EL）。
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