Nanoparticle-based delivery enhances anti-inflammatory effect of low molecular weight heparin in experimental ulcerative colitis.

Drug Delivery
Tawfek YazejiAlf Lamprecht

Abstract

Epithelial administration of low molecular weight heparin (LMWH) has proven its therapeutic efficiency in ulcerative colitis (UC) but still lacks of a sufficiently selective drug delivery system. Polymeric nanoparticles were used here not only to protect LMWH from intestinal degradation but also to provide targeted delivery to inflamed tissue in experimental colitis mice. LMWH was associated with polymethacrylate nanoparticles (NP) type A (PEMT-A) or type B (PEMT-B) of a size: 150 nm resulting in a maximum drug loading: 0.1 mg/mg. In a lipopolysaccharide-stimulated macrophages both, free LMWH and LMWH-NP have significantly reduced the cytokines secretion independently from cellular uptake. The in-vivo therapeutic efficiency was dose dependent as at low doses (100 IU/kg) only minor differences between free LMWH and LMWH-NP were found and the superiority of LMWH-NP became prominent with dose increase (500 IU/kg). Administration of LMWH-NP at 500 IU/kg has markedly improved the clinical activity as compared to LMWH while similarly pathophysiological indicators revealed increased therapeutic outcome in presence of NP compared to LMWH alone: Myeloperoxidase (Colitis control: 10 480 ± 5335, LMWH-PEMT-A NP: 1507 ± 2165, LMWH-PEMT-B NP...Continue Reading

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Citations

Jul 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fahad AkhtarShuying He
Mar 21, 2020·Current Topics in Medicinal Chemistry·Prasad MinakshiPreeti Lakhani
Aug 15, 2020·Drug Delivery and Translational Research·Eleonora ScarcelloYann Pellequer
Jul 1, 2020·Advanced Healthcare Materials·Sufeng ZhangGiovanni Traverso
Jul 23, 2020·Advanced Drug Delivery Reviews·Romain BrusiniPatrick Couvreur
Feb 14, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Anas AhmadRehan Khan
Mar 9, 2021·Frontiers in Bioengineering and Biotechnology·Huailan WangSifeng Tao

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