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

Ulcerative colitis (UC) is a chronic inflammation-relateddiseasethat severely affects the colon and rectum regions. A variety of therapyregimens are used for the treatment of UC. Clinically, therapeuticenema is the choice of therapy for UC patients. Irrespective of on-siteadministration, the major limitation of therapeutic enemas is thedispossession of the medicine followed by low drug availability forthe therapeutic action. In our present work, we have developed anenzyme-responsive injectable hydrogel (ER-hydrogel) to overcome thelimitations of therapeutic enema. The hydrogels possess two majoradvantages, which are being exploited for therapeutic drug deliveryin UC: prolonged retention and enzyme responsiveness. The former isone of the prominent advantages of hydrogel compared to free drugenema and the latter controls the release of the drug or providesdrug release on-demand. The ER-hydrogel was formulated by the heat-coolmethod and for therapeutic purposes, a corticosteroid drug, budesonide(Bud), was encapsulated into the ER-hydrogel and evaluated for itsvarious physicochemical and therapeutic potentials in dextran sodiumsulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirmthe retention or mucoadhesive nature of the ER-hydrogel, and the upsurgein Bud release from the Bud-loaded ER-hydrogel upon the addition ofesterase enzyme confirms the enzyme-mediated drug release from theER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promisingresults in alleviating the disease activity index of UC, and restoredthe length of the colon, which is the main hallmark of UC. In termsof the health of the colon tissue, the Bud-loaded ER-hydrogel restoredthe colonic tissue damage, as seen in the H & E-stained, AB-NR-stained,and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogelalso markedly subsided the IL-1 & beta;, TNF-& alpha;, MPO, and nitritelevels in serum and colon tissues. Thus, the fabricated Bud-loadedER-hydrogel possesses appreciable translational potential due to itsability to significantly ameliorate inflammatory changes comparedto naive or water-based therapeutic enema in acute experimental colitisin mice.