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达沙替尼固体自微乳化给药系统的优化、评价和评估。

Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, , and assessment.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.

Department of Biological Sciences, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.

出版信息

Ther Deliv. 2024;15(10):749-768. doi: 10.1080/20415990.2024.2397330. Epub 2024 Sep 17.

Abstract

Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated. I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, release and permeation, cell-based assays and pharmacokinetic study. DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. pharmacokinetic study revealed 1.94-fold increment in AUC for the DST-S-SNEDDS group than free DST. S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

摘要

达沙替尼(DST)是一种口服酪氨酸激酶抑制剂,水溶性差。为了解决这个问题,我们设计了一种达沙替尼的固体自微乳给药系统(S-SNEDDS)。采用 I-最优混合设计,以芳樟醇、吐温 RH40 和 Transcutol P 为载药材料对载达沙替尼 SNEDDS 进行优化。对 S-SNEDDS 进行了理化性质表征、释放度和渗透性、基于细胞的测定和药代动力学研究。DST-S-SNEDDS 的粒径和 PDI 分别为 141.53±5.371nm 和 0.282±0.020。DST-S-SNEDDS 在 MDA-MB-231 中的 IC (1.825μg/mL)明显低于游离 DST(7.298μg/mL)。药代动力学研究表明,DST-S-SNEDDS 组的 AUC 比游离 DST 组增加了 1.94 倍。S-SNEDDS 可能是提高达沙替尼生物利用度和疗效的有前途的方法。

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