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  • Title: Chitosan nanoconstructs for improved oral delivery of low molecular weight heparin: In vitro and in vivo evaluation.
    Author: Paliwal R, Paliwal SR, Agrawal GP, Vyas SP.
    Journal: Int J Pharm; 2012 Jan 17; 422(1-2):179-84. PubMed ID: 22079712.
    Abstract:
    The aim of present study was to investigate the potential of mucoadhesive polymer chitosan (CS) and N-trimethyl chitosan (TMC) based nanoparticulate systems for oral bioavailability enhancement of low molecular weight heparin (LMWH). The TMC was synthesized by methylation of chitosan followed by characterization using infrared spectroscopy and (1)H-NMR spectroscopy. The IR and NMR spectra of TMC confirmed the presence of trimethyl groups and estimated the degree of quaternization for TMC about 46%. TMC nanoparticles were then prepared by ionic gelation method. The developed CS-NPs and TMC-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency, in vitro release behavior and storage stability at different temperature and simulated gastrointestinal tract conditions. The fluorescent microscopy study confirmed the higher particle uptake of TMC-NPs by gastrointestinal epithelium in comparison to the CS-NPs. The concentration of LMWH in the systemic circulation followed by oral administration of formulations was estimated using FXa chromogenic assay. A significant increase (p<0.05) in the oral bioavailability of LMWH was observed with TMC-NPs than both CS-NPs as well as plain LMWH solution. These findings suggested that TMC nanoparicles hold promise for oral delivery of LMWH and clinical applicability for the treatment of vascular disorders like deep vein thrombosis and pulmonary embolism, etc.
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