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.
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)
作者简介
Corresponding authors:Senlin Shi,Tel./fax:+8657186613524,E-mail addresses:pjstone@163.com;Corresponding authors:Ruxandra Gref,ruxandra.gref@universite-paris-saclay.fr;Corresponding authors:Jiwen Zhang,+862150805901,jwzhang@simm.ac.cn;The authors made equal contributions to this work:Kena Zhao;The authors made equal contributions to this work:Tao Guo;The authors made equal contributions to this work:Caifen Wang
