Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery  

作　　者：Kena Zhao Tao Guo Caifen Wang Yong Zhou Ting Xiong Li Wub Xue Li Priyanka Mittal Senlin Shi Ruxandra Gref Jiwen Zhang 

机构地区：[1]College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 311402,China [2]Center for Drug Delivery System,Shanghai Institute of Materia Medica,State Key Laboratory of Drug Research,Chinese Academy of Sciences,Shanghai 201203,China [3]NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China [4]Key Laboratory of Modern Chinese Medicine Preparations,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China [5]Universite´Paris-Saclay,CNRS 8214,Institut des Sciences Mole´culaires d’Orsay,Orsay 91405,France [6]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第9期1709-1718,共10页药学学报（英文版）

基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA12050307,China);the ANR AntiTBnano project(ANR-14-CE08-0017,France);the National Research Council of Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09721002e009,China)

摘　　要：It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases.When the inhalable micron-sized crystals ofγ-cyclodextrin metal-organic framework(CD-MOF)was utilized as dry powder inhalers(DPIs)carrier with high fine particle fraction(FPF),it was found in this research that the encapsulation of a glycoside compound,namely,scutellarin(SCU)in CD-MOF could significantly enhance its laryngeal deposition.Firstly,SCU loading into CD-MOF was optimized by incubation.Then,a series of characterizations were carried out to elucidate the mechanisms of drug loading.Finally,the laryngeal deposition rate of CD-MOF was 57.72±2.19%improved by SCU,about two times higher than that of CD-MOF,when it was determined by Next Generation Impactor(NGI)at 65 L/min.As a proof of concept,pharyngolaryngitis therapeutic agent dexamethasone(DEX)had improved laryngeal deposition after being co-encapsulated with SCU in CDMOF.The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF,which defined the enhanced laryngeal anchoring.In conclusion,the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.

关 键 词：Laryngeal delivery g-Cyclodextrin metalorganic framework SCUTELLARIN DEXAMETHASONE Molecular simulation 

分 类 号：R943[医药卫生—药剂学]