Abstract
Low molecular weight heparin (LMWH) is reported to have therapeutic action on ulcerative colitis (UC). To facilitate its oral administration and improve the colon-targeting property, LMWH-loaded nanoparticles (TMC-NPs and SA-TMC-NPs) are prepared and evaluated by a series of studies, including their stabilities, drug release profiles, mucosal permeation, mucoadhesion, cytotoxicities, cellular uptake profiles, anticoagulant and anti-inflammatory activities, mucosal healing properties, biosafety and ameliorative effects on experimental colitis. Consequently, oral administration of LMWH-loaded NPs for 5 days perform significant therapeutic effects on mice, which are manifested as improved body weight gains, colon length, DAI score, MPO activity and histological characteristics. Besides, SA-TMC-NPs show better colon-targeting property than TMC-NPs that is demonstrated by lower oral absorption (ATPP 38.95 s) and stronger mucoadhesion (kcps reduces 36.46 %) to inflamed colon tissues. Therefore, TMC-based NPs are proved to be as promising oral colon-targeting drug delivery systems of LMWH and has potential application in UC treatment.
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