Browsing by Author "Sonia, TA"

Now showing 1 - 7 of 7
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    Bioadhesive Hydrophobic Chitosan Microparticles for Oral Delivery of Insulin: In Vitro Characterization and In Vivo Uptake Studies
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2011) Sonia, TA; Rekha, MR; Sharma, CP
    Hydrophobically modified polymeric matrices for drug delivery were developed by N-acylation of chitosan with long(C-18) and medium chain(C-8) fatty acid chlorides like octanoyl and oleoyl chloride. Chemical modifications of chitosan were confirmed by IR spectra and trinitrobenzenesulphonic acid assay. Modified chitosan particles were prepared by ionotropic gelation with sodium tripolyphosphate. Hydrophobic modification was confirmed by contact angle measurements. Scanning electron micrographs showed the presence of compact microparticles. Swelling studies showed that oleoyl chitosan exhibited low swelling profile than octanoyl chitosan at acidic pH. In vitro release profile at pH 7.4 showed that about 90% of insulin was released by 5th hour. ELISA studies proved that the microparticles were capable of maintaining biological activity of insulin. Mucoadhesion studies proved that oleoyl derivative was more mucoadhesive than octanoyl derivative. In vivo uptake studies of fluorescent-labeled microparticles on rat intestinal sections showed that oleoyl chitosan microparticles exhibited significant uptake than octanoyl chitosan. These results suggests that oleoyl moiety would resist degradation by the gastric enzymes and will enhance mucoadhesivity through hydrophobic interactions and also the permeability by loosening the tight junctions, thus making it a useful carrier for oral peptide delivery applications. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2902-2910, 2011
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    Chitosan and Its Derivatives for Drug Delivery Perspective
    (CHITOSAN FOR BIOMATERIALS I, 2011) Sonia, TA; Sharma, CP
    Biopolymers are promising materials in the delivery of protein drugs due to their compatibility, degradation behavior, and nontoxic nature on administration. On suitable chemical modification, these polymers can provide better materials for drug delivery systems. Nanostructured drug carriers allow the delivery of not only small-molecule drugs but also of nucleic acids and proteins. The use of biopolymers like dextran, starch, alginate, and pullulan nanoparticles in drug delivery are briefly discussed. Being the only cationic polysaccharide of natural origin, chitosan, a versatile biopolymer of the aminoglucopyran family is being extensively explored for various biomedical and pharmaceutical applications such as drug delivery. In this review, we aim to comprehensively integrate the recent applications of chitosan nano/microparticles in oral and/or buccal delivery, stomach-specific drug delivery, intestinal delivery, colon-specific drug delivery, and gene delivery, giving special emphasis to oral drug delivery.
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    In vitro evaluation of N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan for oral insulin delivery
    (CARBOHYDRATE POLYMERS, 2011) Sonia, TA; Sharma, CP
    The present investigation explores an oral insulin delivery system based on the modification of chitosan, N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan (HTCC). Synthesis of HTCC was carried out by coupling glycidyl trimethylammonium chloride (GTAC) to chitosan in aqueous medium. Quaternization was confirmed by TNBS assay, FTIR, NMR, SEM studies and zeta potential analysis. Cytotoxicity studies of the derivative were carried out by mu assay and release profile of insulin from HTCC matrix was monitored under in vitro experimental conditions. Further biological activity and conformational stability of released insulin were confirmed using ELISA and circular dichroism studies. Adhesion studies on mucin and freshly excised rat intestinal sections were carried out to evaluate the mucoadhesive nature of the matrix. Confocal microscopy observations showed that these microparticles were capable of opening tight junctions. By exploiting the mucoadhesive and controlled drug releasing capabilities, HTCC particles seems to be a promising candidate for oral insulin delivery. (C) 2010 Elsevier Ltd. All rights reserved.
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    In vitro evaluation of quaternized polydimethylaminoethylmethacrylate sub-microparticles for oral insulin delivery
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2013) Sonia, TA; Sharma, CP
    This investigation describes the synthesis and in vitro evaluation of cationic hydrogel sub-microparticles based on polydimethylaminoethylmethacrylate for oral insulin delivery. Polymerization of dimethylaminoethylmethacrylate was carried out in aqueous medium with potassium persulfate as the initiator. Quaternization of the resulting hydrogel was carried out to introduce cationic surface groups and the derivatization was confirmed by zeta potential measurements, nuclear magnetic resonance and infrared spectroscopies. Swelling behavior of these particles was evaluated for dependence of pH. Insulin-loaded particles were subjected to in vitro release experiments at gastric and intestinal pH. Moreover, cytotoxicity evaluation showed that both polydimethylaminoethylmethacrylate and its quaternized derivative were non-toxic to Caco-2 and L929 cell lines. The presence of quaternary ammonium groups improved the cationic charge and enhanced the mucoadhesive properties of the hydrogel. Confocal microscopic observations showed that these sub-microparticles were capable of opening tight junctions between the Caco-2 cells and thus increased the paracellular permeability. The above studies suggest that cationic hydrogel sub-microparticles can act as a good candidate for oral insulin delivery.
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    In Vitro Evaluation of Thiolated Polydimethylaminoethylmethacrylate Hydrogel Sub-Microparticles for Oral Insulin Delivery
    (JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 2013) Sonia, TA; Sharma, CP
    In this investigation, novel cationic thiomer, Thiolated polydimethylaminoethylmethacrylate (PDCys) is synthesised and the feasibility of PDCys sub-microparticles as oral insulin delivery carriers is evaluated in vitro. The presence of both positive charge and thiol group in the same matrix plays a vital role in improving the paracellular permeability. Thiol groups interacts with cysteine rich subdomains via disulfide bond formation and positive charge interacts with sialic residues of mucus glycoproteins via electrostatic interaction, thereby increasing the mucoadhesivity. Cytotoxic evaluation by MTT assay shows that PDCys is nontoxic. Force and Work of adhesion of PDCys was found found to be higher than that of parent polymer. ELISA and Circular dichroism spectra confirms that PDCys retains the biological activity and conformation of insulin. Moreover, PDCys is capable of opening the tight junctions by actin and occludin filament dislocation. Furthermore, permeation of FD4 on Caco-2 cells is improved by 3.9 fold compared to the parent polymer. Preliminary studies suggest that thiolated particles can serve as potential vehicles for oral insulin delivery.
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    N-hydroxypropyltrimethylammonium polydimethylaminoethylmethacrylate sub-microparticles for oral delivery of insulin-An in vitro evaluation
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2013) Sonia, TA; Sharma, CP
    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. (C) 2013 Elsevier B.V. All rights reserved.
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    pH Sensitive Thiolated Cationic Hydrogel for Oral Insulin Delivery
    (JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 2014) Sonia, TA; Sharma, CP
    The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3 +/- 1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.