Use of ordered mesoporous silica-loaded phyto-phospholipid complex for BCS IV class plant drug to enhance oral bioavailability: a case report of tanshinone IIA
Use of ordered mesoporous silica-loaded phyto-phospholipid complex for BCS IV class plant drug to enhance oral bioavailability: a case report of tanshinone IIA
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使用有序介孔二氧化硅负载植物磷脂复合物用于BCS IV类植物药物以提高口服生物利用度：丹参酮IIA的病例报告
DOI：
10.1039/c6ra22778c
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Di, Liuqing
中科院分区：
文献类型：
--
作者：
Chen, Ting;Yang, Junhui;Di, Liuqing
本研究以丹参酮IIA（TS）为模型药物，旨在通过构建由磷脂复合物（PC）和有序介孔二氧化硅基固体分散体（SD）组成的联合给药系统（CDDS），提高一种生物药剂学分类系统（BCS）IV类植物药的膜通透性及体外溶出速率，进而提升其口服生物利用度。采用溶剂蒸发法制备了丹参酮IIA磷脂复合物（TS - PC）和有序介孔二氧化硅基固体分散体（TSPC - SD）。差示扫描量热法（DSC）、粉末X射线衍射（PXRD）和傅里叶变换红外光谱（FTIR）证实了TS - PC或TSPC - SD的形成，以及这两种体系中无定形形态的存在。正辛醇/水分配系数（lg P - o/w）测试表明，与未制成制剂的TS相比，TS - PC的lg P - o/w显著降低，而TSPC - SD与TS - PC相比则未见升高。在Caco - 2细胞单层模型中的评估显示，与未制成制剂的TS相比，TS - PC的表观渗透系数（P - app）所体现的吸收通透性显著增加（p < 0.05），提高了70.2%。与未制成制剂的TS相比，TSPC - SD中TS的体外药物溶出速率显著提高（p < 0.01），而TS - PC中TS的体外药物溶出速率则略有下降。药代动力学研究表明，与未制成制剂的TS相比，TSPC - SD的AUC(0 - t) 高出2.19倍（p < 0.01）。使用TSPC - SD后生物利用度的显著提升可能源于综合效应，包括通过PC改善lg P - o/w和P - app，以及通过SD提高溶出速率。这些结果表明，该CDDS有望提高BCS IV类药物的口服生物利用度。
This work aimed to improve membrane permeability as well as in vitro dissolution rate and thus enhance oral bioavailability for a BCS IV class plant drug by constructing a combined drug delivery system (CDDS) composed of a phospholipid complex (PC) and an ordered mesoporous silica-based solid dispersion (SD), using tanshinone IIA (TS) as a model drug. Tanshinone IIA phospholipid complex (TS–PC) and ordered mesoporous silica-based solid dispersion (TSPC-SD) were prepared using the solvent evaporation method. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy proved the formation of TS–PC or TSPC-SD, and amorphous form existing in these two systems. n-Octanol/water partition coefficient (lg Po/w) tests showed that a remarkably decreased lg Po/w for TS–PC was obtained compared to unformulated TS, while no increase was observed for TSPC-SD compared to TS–PC. Evaluations in Caco-2 cell monolayers revealed that TS–PC exhibited a significantly increased absorptive permeability (p < 0.05) in apparent permeability coefficients (Papp) (70.2% higher) compared to unformulated TS. Compared to that of unformulated TS, in vitro drug dissolution rate of TS from TSPC-SD significantly increased (p < 0.01), while that from TS–PC was slightly decreased. Pharmacokinetic studies demonstrated that TSPC-SD had 2.19-fold higher AUC0–t compared to unformulated TS (p < 0.01). The remarkable improvements in bioavailability with the use of TSPC-SD may result from comprehensive effects, including improved lg Po/w and Pappvia PC, and increased dissolution rates from SD. These results indicated that the CDDS can be promising for enhancing the oral bioavailability of BCS IV class drugs.