Colon-Adhering Delivery System with Inflammation Responsiveness for Localized Therapy of Experimental Colitis

灌肠 自愈水凝胶 药物输送 药品 治疗效果 药理学 治疗指标 体内 溃疡性结肠炎 结肠炎 布地奈德 医学 右旋糖酐 炎症性肠病 靶向给药 化学 材料科学 免疫学 外科 内科学 皮质类固醇 疾病 生物 生物化学 纳米技术 有机化学 生物技术
作者
Ajay Kumar,Kanika,Vibhu Kumar,Anas Ahmad,Rakesh K. Mishra,Ahmed Nadeem,Nahid Siddiqui,Md. Meraj Ansari,Syed Shadab Raza,Kanthi Kiran Kondepudi,Rehan Khan
出处
期刊:ACS Biomaterials Science & Engineering [American Chemical Society]
卷期号:9 (8): 4781-4793 被引量:14
标识
DOI:10.1021/acsbiomaterials.3c00480
摘要

Ulcerative colitis (UC) is a chronic inflammation-related disease that severely affects the colon and rectum regions. A variety of therapy regimens are used for the treatment of UC. Clinically, therapeutic enema is the choice of therapy for UC patients. Irrespective of on-site administration, the major limitation of therapeutic enemas is the dispossession of the medicine followed by low drug availability for the therapeutic action. In our present work, we have developed an enzyme-responsive injectable hydrogel (ER-hydrogel) to overcome the limitations of therapeutic enema. The hydrogels possess two major advantages, which are being exploited for therapeutic drug delivery in UC: prolonged retention and enzyme responsiveness. The former is one of the prominent advantages of hydrogel compared to free drug enema and the latter controls the release of the drug or provides drug release on-demand. The ER-hydrogel was formulated by the heat-cool method and for therapeutic purposes, a corticosteroid drug, budesonide (Bud), was encapsulated into the ER-hydrogel and evaluated for its various physicochemical and therapeutic potentials in dextran sodium sulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirm the retention or mucoadhesive nature of the ER-hydrogel, and the upsurge in Bud release from the Bud-loaded ER-hydrogel upon the addition of esterase enzyme confirms the enzyme-mediated drug release from the ER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promising results in alleviating the disease activity index of UC, and restored the length of the colon, which is the main hallmark of UC. In terms of the health of the colon tissue, the Bud-loaded ER-hydrogel restored the colonic tissue damage, as seen in the H&E-stained, AB-NR-stained, and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogel also markedly subsided the IL-1β, TNF-α, MPO, and nitrite levels in serum and colon tissues. Thus, the fabricated Bud-loaded ER-hydrogel possesses appreciable translational potential due to its ability to significantly ameliorate inflammatory changes compared to naive or water-based therapeutic enema in acute experimental colitis in mice.
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