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  • Title: N-hydroxypropyltrimethylammonium polydimethylaminoethylmethacrylate sub-microparticles for oral delivery of insulin--an in vitro evaluation.
    Author: Sonia TA, Sharma CP.
    Journal: Colloids Surf B Biointerfaces; 2013 Jul 01; 107():205-12. PubMed ID: 23500732.
    Abstract:
    The present study describes the synthesis and in vitro evaluation of quaternised polydimethylaminoethylmethacrylate for oral delivery of insulin. Quaternisation of the polymer was carried out by conjugating N-hyroxypropyltrimethylammonium chloride to aminoterminated polydimethylaminoethylmethacrylate. Quaternised particles were characterised by particle size, zeta potential measurements, nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), differential scanning calorimetry (DSC) and atomic force microscopy (AFM). In addition, in vitro insulin release experiments, cytotoxic evaluation on L929 & Caco-2 cells, mucoadhesion, enzymatic degradation and tight junction visualisation studies were also performed to evaluate the potential of this matrix for oral delivery of insulin. Results suggest that the quaternised particles exhibited positive zeta potential with a particle size of 513.6±17 nm. Dose-dependent cytotoxic evaluation of quaternised particles on L929 & Caco-2 cells confirmed the nontoxic nature of the matrix. Quaternised particles were more mucoadhesive compared to parent polymer. Adhesive behaviour of mucin with quaternised particles were confirmed by DSC. Moreover these particles exhibited calcium chelating ability and displayed significant inhibitory effect towards trypsin and chymotrypsin. These particles also helped in the opening of tight junctions by disruption of actin filaments and binding to Zona Occludens (ZO-1) proteins. Preliminary studies suggest that the quaternised particles can act as suitable candidates for oral delivery of insulin.
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