Enteric-coated gelatin nanoparticles mediated oral delivery of 5-aminosalicylic acid alleviates severity of DSS-induced ulcerative colitis

被引:65
作者
Ahmad, Anas [1 ]
Ansari, Md Meraj [1 ]
Mishra, Rakesh Kumar [1 ]
Kumar, Ajay [1 ]
Vyawahare, Akshay [1 ]
Verma, Rahul Kumar [1 ]
Raza, Syed Shadab [2 ,3 ]
Khan, Rehan [1 ]
机构
[1] Inst Nano Sci & Technol, Habitat Ctr, Dept Nanotherapeut, Phase 10,Sect 64, Mohali 160062, Punjab, India
[2] Eras Lucknow Med Coll Hosp, Dept Biotechnol, Lab Stem Cell & Restorat Neurol, Lucknow 226003, Uttar Pradesh, India
[3] Era Univ, Dept Stem Cell Biol & Regenerat Med, Lucknow 226003, Uttar Pradesh, India
来源
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2021年 / 119卷
关键词
Ulcerative colitis; Enteric coating; Nanoparticles; 5-Amino salicylic acid; Inflammation; NITRIC-OXIDE; MURINE MODEL; MAST-CELL; INFLAMMATION; THERAPY; SODIUM; SERUM; COX-2; MYELOPEROXIDASE; METABOLISM;
D O I
10.1016/j.msec.2020.111582
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Ulcerative colitis (UC) is an inflammatory condition involving ulcers in colon and rectum. Conventional treatments for colitis confront serious limitations like off target systemic side effects, drug degradation and inactivation, restricted absorption and other complications culminating in poor bioavailability. These limitations necessitate localized drug delivery to inflamed colon such that drug can bypass abrasive gastric surroundings, availing protection form gastric acid and has selective access to colonic mucosa. Therefore, present study was designed to formulate Eudragit-S100 coated 5-amino salicylic acid (5-ASA)-loaded gelatin nanoparticles (NPs) for localized delivery of 5-ASA for treatment of ulcerative colitis. NPs were formulated by nanoprecipitation and solvent evaporation method, had hydrodynamic diameter of 225-250 nm, smooth and spherical surface morphology under TEM, SEM and AFM. Oral administration of NPs ameliorated disease activity indices like fecal occult bleeding, colon length and stool consistency. NPs treatment significantly reduced mast cells infiltration in colon, restored protective mucin layer and appreciably reinstated colonic histoarchitecture. Furthermore, inflammatory biomarkers like TNF-alpha, IL1-beta, COX-2, iNOS, myeloperoxidase and nitrite levels were also significantly reduced by NPs treatment. Overall, results of this study indicate that 5-ASA NPs possessed superior therapeutic efficacy over free 5-ASA in experimental colitis and these results are attributed to their ability to significantly suppress inflammation.
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页数:14
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