Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis  

作　　者：Mahira Zeeshan Qurat Ul Ain Benno Weigmann Darren Story Bryan R.Smith Hussain Ali 

机构地区：[1]Department of Pharmacy,Faculty of Biological Sciences,Quaid-i-Azam University,Islamabad 45320,Pakistan [2]Department of Medicine 1,University of Erlangen-Nuremberg,Kussmaul Campus for Medical Research,Erlangen 91052,Germany [3]Biomedical Engineering Department,Michigan State University,East Lansing 48824,USA [4]Institute for Quantitative Health Science and Engineering,Michigan State University,East Lansing 48824,USA [5]Faculty of Pharmacy,Capital University of Science and Technology,Islamabad 44000,Pakistan

出　　处：《Asian Journal of Pharmaceutical Sciences》2023年第4期124-141,共18页亚洲药物制剂科学（英文）

基　　金：the Higher Education Commission of Pakistan for the provision of HEC Indigenous scholarship (PIN No. 315-12214-2BS3-132) for the research work;the provision of grant under HEC NRPU project No. 9272/Federal/NRPU/R&D/HEC/2017

摘　　要：Ulcerative colitis(UC)is a type of inflammatory bowel disease characterized by inflammation,ulcers and irritation of the mucosal lining.Oral drug delivery in UC encounters challenges because of multifaceted barriers.Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes(Dexa-GP/ES/Pu NCs)have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota,and an underneath galactosylated-PLGA core(GP).The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C(MGL-2)surface receptor.Therefore,both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake.Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs.The nanocargoes were tested using in vitro,ex vivo techniques and dextran sodium sulfate(DSS)induced UC model.Prepared nanocargoes had desired physicochemical properties,drug release,cell uptake and cellular viability.Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2,and restoration of clinical,histopathological,biochemical indices,antioxidant balance,microbial alterations,FTIR spectra,and epithelial junctions’integrity.Thus,Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.

关 键 词：Galactosylated nanocargoes pH-sensitive drug delivery PULLULAN Microbial sensitive Ulcerative colitis Macrophage galactose type-lectin C 

分 类 号：R943[医药卫生—药剂学]