Simultaneous solubilization and extended release of insoluble drug as payload in highly soluble particles of γ-cyclodextrin metal-organic frameworks

被引：27

作者：

Liu, Yujie ^{[1
,2
]}

Zhou, Panpan ^{[2
,5
]}

Cao, Zeying ^{[2
,3
]}

Liang, Wanhui ^{[1
]}

Yan, Jiazhi ^{[1
]}

Xu, Huipeng ^{[2
,3
]}

Wu, Li ^{[2
,4
]}

Sun, Lixin ^{[5
]}

Gong, Likun ^{[6
]}

Peng, Can ^{[1
,4
]}

Guo, Tao ^{[2
]}

Wang, Caifen ^{[2
]}

Zhang, Jiwen ^{[1
,2
]}

机构：

[1] Anhui Univ Chinese Med, Sch Pharm, Hefei 230012, Peoples R China

[2] Chinese Acad Sci, Ctr Drug Delivery Syst, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Anhui Prov Key Lab Pharmaceut Preparat Technol &, Hefei 230012, Peoples R China

[5] Shenyang Pharmaceut Univ, Sch Pharm, Wenhua Rd 103, Shenyang 110016, Peoples R China

[6] Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Beijing, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2022年 / 619卷

基金：

国家重点研发计划; 美国国家科学基金会;

关键词：

Cyclodextrin-metal organic framework; 18 beta-glycyrrhetinic acid; Biphasic release; Molecular modeling; PULMONARY-FIBROSIS; ACID; LICORICE; PROGRESS;

D O I：

10.1016/j.ijpharm.2022.121685

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The inclusion and nanocluster formed in cyclodextrin-metal organic framework (CD-MOF) make it a remarkable vehicle in improving the solubility and bioavailability of insoluble drugs, but rarely in elongation of drug release kinetics. In this research, an insoluble compound, 18 beta-glycyrrhetinic acid (GA), encapsulated in CD-MOF (GA@nano-CD-MOF) had prominent effects in the treatment of bleomycin-induced idiopathic pulmonary fibrosis in rats with an enhanced bioavailability by 6.8 times. The solubility of GA@nano-CD-MOF was 7780 times higher than that of GA, which was explained by the solubility parameter of amorphous cells constructed in silico simulation. CD-MOF imparted GA unique biphasic release kinetics, namely, GA released instantly to 52% and slowly released to 100% for a period of 5 days, which made the drug loaded particles much more flexible in pharmaceutical applications. The distribution of GA molecules in CD-MOF and drug loading priority obtained by molecular docking illustrated the formation of biphasic release mode at the molecular level combined with other characterizations of SEM, PXRD, TGA and DSC. In conclusion, CD-MOF has a unique effect to simultaneously solubilize an insoluble drug and extend its release for days as payload in highly soluble particles of.-cyclodextrin metal-organic frameworks, which broaden the applications of drugs in specific treatment and then enhance the therapeutic effects.

引用

页数：11

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