Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy  

作　　者：Yu Tang Lanfang Zhang Rui Sun Baiyi Luo Yu Zhou Yan Zhang Yuqi Liang Bo Xiao Chenhui Wang 

机构地区：[1]Chongqing Key Laboratory of Natural Product Synthesis and Drug Research,Innovative Drug Research Center,School of Pharmaceutical Sciences,Chongqing University,Chongqing 401331,China [2]State Key Laboratory of Silkworm Genome Biology,College of Sericulture,Textile and Biomass Sciences,Southwest University,Chongqing 400715,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2023年第4期153-161,共9页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.52273123);the Graduate Scientific Research and Innovation Foundation of Chongqing,China(No.CYS21072);the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0344,cstc2021jcyj-msxmX0342);the Open Research Project from State Key Laboratory of Silkworm GenomeBiology(No.SKLSGB-orp202010).

摘　　要：The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR.The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus layer.The QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties.Fluorescence recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model.Notably,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory tract.Themicemelanoma lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in vivo.PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.

关 键 词：Pulmonary drug delivery Mucus penetration QUERCETIN Pluronic F127 

分 类 号：R943[医药卫生—药剂学]