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Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

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Chinese Chemical Letters 2023年第1期34卷 245-250页

作者： Yuan He Chang Liu Run Han Yingmin Liang judith choi wo mak Yinghao Zhu Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China LKS Faculty of Medicine Department of MedicineThe University of Hong KongHong KongChina Institute of Applied Physics and Materials Engineering University of MacaoMacaoChina

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory ***,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the *** this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary *** LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization *** prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked *** results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid ***,the macrophages clearance was also impeded by this Lipo-NCs *** vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of *** pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic *** conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

关键词： Pulmonary delivery Lipid-coated nanocrystals Cell uptake Transport Systemic absorption Macrophage clearances

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Size Effect of Curcumin Nanocrystals on Airway Mucosa Penetration, Lung Tissue Distribution and Pharmacokinetics Studies by Pulmonary Delivery

Size Effect of Curcumin Nanocrystals on Airway Mucosa Penetr...

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2018年第十二届中国药物制剂大会

作者：何媛 Yingmin Liang judith choi wo mak Yonghong Liao Ting Li Ru Yan Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau LKS Faculty of Medicine Department of Medicine The University of Hong Kong Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Applied Physics and Materials Engineering University of Macau

Objective: Nanocrystal has been introduced for pulmonary delivery of hydrophobic drugs for several years. Although the deposition and bioavailability have been extensively studied, little is known about the absorption process after deposition. The aim of this study is to investigate the size effect of nanocrystals on pulmonary absorption and explore the real time release behavior during this process. Methods: Three different sized curcumin nanocrystals were fabricated by wet milling and anti-solvent precipitation method. The in vitro dissolution, mucus diffusion and Calu-3 uptake and transport studies were investigated. The real time release behavior was studied by the applying of FRET technology. Then the in vivo lung retention and distribution were conducted by drug concentration measurement and fluorescence observing in lung tissue sections after pulmonary administration. The pharmacokinetics study was performed by plasma concentration measurement with LC/MS. Results: The prepared nanocrystals were about 200 nm, 500 nm and 1000 nm with crystal characters. The in vitro dissolution and simulated mucus diffusion studies showed a size depended manner, where the smallest sized nanocrystal exhibited a rapid dissolution velocity and higher diffusion percentage. The Calu-3 cell studies demonstrated that smaller sized nanocrystals displayed higher uptake and transport efficiency. The result of real time dissolution behavior displayed that FRET efficiency decreased continuously from mucus to cells, which demonstrated the nanocrystals dissolved gradually during this process and penetrated through lung epithelium layer mainly by free drug form. The in vivo lung retention determination and histological studies showed that large sized nanocrystals remained higher amount in lung tissue, while small sized absorbed rapidly into blood system. The plasma pharmacokinetics study showed the AUC of small sized nanocrystal was 1.75 and 3.32 times greater than middle and large nanocrysta

关键词： Pulmonary delivery nanocrystals size effect FRET lung absorption

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