Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation

doi:10.1016/j.ijpharm.2021.120825

	Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation
	Zhou, Yong 1,2; Zhang, Meijuan 2,3; Wang, Caifen 2,3; Ren, Xiaohong 2; Guo, Tao 2; Cao, Zeying 2,4; Zhang, Jiwen 1,2; Sun, Lixin 3; Wu, Li 2
刊名	INTERNATIONAL JOURNAL OF PHARMACEUTICS
	2021-09-05
卷号	606 页码:9
关键词	D-Limonene gamma-cyclodextrin metal-organic framework Dry powder inhaler Solidification Aerosolization Bioavailability
ISSN号	0378-5173
DOI	10.1016/j.ijpharm.2021.120825
通讯作者	Sun, Lixin(slx04@163.com) ; Wu, Li(wuli@simm.ac.cn)
英文摘要	D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve efficient pulmonary delivery, herein, D-Lim was loaded into biodegradable gamma-cyclodextrin metal-organic framework (gamma-CD-MOF) with optimal loading efficiency achieving 13.79 +/- 0.01% (molar ratio of D-Lim and gamma-CD-MOF was 1.6:1), which possessed cubic shape with controllable particle size (1-5 mu m). The experimental results indicated that gamma-CD-MOF could improve the stability of D-Lim. A series of characterizations and molecular docking were used to reveal the interaction between D-Lim and gamma-CDMOF. The solidification of D-Lim by gamma-CD-MOF played a crucial role in the exploitation of its inhalable dosage form, dry powder inhaler (DPI). Specifically, the aerosolization of D-Lim@gamma-CD-MOF for inhalation was satisfactory with a fine particle fraction (FPF) of 33.12 +/- 1.50% at 65 L/min of flow rate. Furthermore, in vivo study had shown a 2.23-fold increase in bioavailability of D-Lim solidified by gamma-CD-MOF for inhalation compared to D Lim for oral administration. Therefore, it is considered that gamma-CD-MOF could be an excellent carrier for pulmonary drug delivery to realize solidification and lung therapeutic effects of volatile oils.
资助项目	Research Foundation of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120182001] ; Key Program for International Science and Technology Cooperation Projects of China[2020YFE0201700] ; National Science and Technology Major Projects for the Major New Drugs Innovation and Development[2018ZX09721002-009]
WOS关键词	STABILITY ; CD ; ENCAPSULATION ; NANOCARRIERS ; INFLAMMATION ; FORMULATION ; COMPONENTS ; RELEASE ; CARRIER
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000692239100002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297847]
专题	中国科学院上海药物研究所
通讯作者	Sun, Lixin; Wu, Li
作者单位	1.Jiangxi Univ Chinese Med, Sch Pharm, Nanchang 330004, Jiangxi, Peoples R China 2.Chinese Acad Sci, Ctr Drug Delivery Syst, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Shenyang Pharmaceut Univ, Sch Pharm, Dept Pharmaceut Anal, 103 Wenhua Rd, Shenyang 110016, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Yong,Zhang, Meijuan,Wang, Caifen,et al. Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2021,606:9.
APA	Zhou, Yong.,Zhang, Meijuan.,Wang, Caifen.,Ren, Xiaohong.,Guo, Tao.,...&Wu, Li.(2021).Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation.INTERNATIONAL JOURNAL OF PHARMACEUTICS,606,9.
MLA	Zhou, Yong,et al."Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation".INTERNATIONAL JOURNAL OF PHARMACEUTICS 606(2021):9.