One-pot synthesis of pH-responsive Eudragit-mesoporous silica nanocomposites enable colonic delivery of glucocorticoids for the treatment of inflammatory bowel disease
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Qu , Z , Wong , K Y , Moniruzzaman , M , Begun , J , Santos , H A , Hasnain , S Z , Kumeria , T , McGuckin , M A & Popat , A 2021 , ' One-pot synthesis of pH-responsive Eudragit-mesoporous silica nanocomposites enable colonic delivery of glucocorticoids for the treatment of inflammatory bowel disease ' , Advanced Therapeutics , vol. 4 , no. 2 , 2000165 . https://doi.org/10.1002/adtp.202000165
| Title: | One-pot synthesis of pH-responsive Eudragit-mesoporous silica nanocomposites enable colonic delivery of glucocorticoids for the treatment of inflammatory bowel disease |
| Author: | Qu, Zhi; Wong, Kuan Yau; Moniruzzaman, Md.; Begun, Jakob; Santos, Hélder A.; Hasnain, Sumaira Z.; Kumeria, Tushar; McGuckin, Michael A.; Popat, Amirali |
| Contributor organization: | Division of Pharmaceutical Chemistry and Technology Helsinki One Health (HOH) Drug Research Program Nanomedicines and Biomedical Engineering Divisions of Faculty of Pharmacy |
| Date: | 2021-02 |
| Language: | eng |
| Number of pages: | 11 |
| Belongs to series: | Advanced Therapeutics |
| ISSN: | 2366-3987 |
| DOI: | https://doi.org/10.1002/adtp.202000165 |
| URI: | http://hdl.handle.net/10138/335107 |
| Abstract: | Oral glucocorticoids are backbones for the acute management of inflammatory bowel disease (IBD). However, the clinical effectiveness of conventional oral dosage forms of glucocorticoids is hindered by their low delivery efficiency and systemic side effects. To overcome this problem, a smart drug delivery system with high loading capacity and colonic release by coating functionalized mesoporous silica nanoparticles (MSNs) with a pH‐responsive polymer Eudragit S100 is proposed. In vitro dissolution tests show that Eudragit‐coated MSNs can limit the burst release of loaded prednisolone and budesonide in the gastric environment with more than 60% of the drugs released only at colonic pH (i.e., pH ≥ 7). In vivo therapeutic efficacy of budesonide‐loaded nanoparticles is tested in a murine model of dextran sodium sulfate‐induced colitis. An oral budesonide dose of 0.2 mg kg−1 nanoparticles with Eudragit coating improves the disease activity index compared to other groups. Interestingly, both coated and uncoated nanoparticles show pathological improvements demonstrated by similar levels of histological colitis score. However, coated nanoparticles significantly decrease mRNA expression of the cytokines (Il‐1β, Il‐17, and Il‐10) particularly in proximal colon, indicating colonic delivery. Overall, this study demonstrates the effectiveness of a simple method to fabricate targeted nanomedicine for the treatment of IBD. |
| Subject: |
BUDESONIDE
ENDOPLASMIC-RETICULUM STRESS Eudragit INFLAMED COLON INTERLEUKIN-10 MCM-41 NANOPARTICLES RELEASE DRUG-DELIVERY SYSTEM T-CELLS TARGETED DELIVERY ULCERATIVE-COLITIS colitis colonic delivery mesoporous silica oral drug delivery 317 Pharmacy 318 Medical biotechnology 221 Nano-technology |
| Peer reviewed: | Yes |
| Usage restriction: | openAccess |
| Self-archived version: | acceptedVersion |
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