Mucoadhesive nanoparticles-based oral drug delivery systems enhance ameliorative effects of low molecular weight heparin on experimental colitis. (15th October 2020)

• Record Type: Journal Article
• Authors: Yan, Yan; Sun, Ying; Wang, Pengchong; Zhang, Rui; Huo, Chuanchuan; Gao, Tingting; Song, Chenghua; Xing, Jianfeng; Dong, Yalin
• Is Part Of: Carbohydrate polymers. Volume 246(2020)
• Publication Date: 2020-10-15
• Subjects: APTT activated partial thromboplastin time -- AUC area under the curve -- CLSM confocal laser scanning microscopy -- CS chitosan -- DAI disease activity index -- DL drug loading -- DLS dynamic light scattering -- DQ degree of quaternization -- EE entrapment efficiency -- FITC fluorescein5(6)-isothiocyanate -- FTIR Fourier transform infrared spectroscopy -- HE hematoxylin and eosin -- 1H NMR proton nuclear magnetic resonance -- Kcps kilo count per second -- LMWH low molecular weight heparin -- MPO myeloperoxidase -- OCDDS oral colon-targeting drug delivery system -- PDI polydispersity index -- PT prothrombin time -- SA sodium alginate -- SA-TMC-NPs alginate coated trimethyl chitosan nanoparticles -- TEM transmission electron microscope -- TMC trimethyl chitosan -- TMC-NPs trimethyl chitosan nanoparticles -- TNBS 24, 6-trinitrobenzenesulfonic acid -- TPP sodium tripolyphosphate -- TT thrombin time -- UC ulcerative colitis -- UFH unfractionated heparin; Ulcerative colitis -- Low molecular weight heparin -- Trimethyl chitosan -- Mucoadhesion -- Colon targeting -- Oral drug delivery; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2020.116660
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Low molecular weight heparin-loaded nanoparticles (LMWH-loaded NPs) are prepared. LMWH-loaded NPs are used for oral therapy of ulcerative colitis (UC). NPs are designed based on the surface charge characteristics of inflamed mucosa. SA-TMC-NPs have desirable mucoadhesion and colon-targeting property. SA-TMC-NPs improve the therapeutic effects of LMWH on UC in colitis mice. 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.