Raghunath Das

Dextrin cross linked with poly(HEMA): a novel hydrogel for colon specific delivery of ornidazole

We report on the synthesis and characterization of a novel hydrogel based on dextrin grafted with poly(2-hydroxyethyl methacrylate) by embedding N,N′-methylene bis acrylamide (MBA) as cross linker, into a polymeric network in the presence of potassium persulphate (KPS) initiator for colon specific delivery of ornidazole. Various grades of hydrogels [Dxt-g-p(HEMA)] have been synthesized by altering the reaction parameters and the best one optimized. The developed hydrogel has been characterized using FTIR spectra, 13C NMR spectra, elemental analysis, XRD study, SEM analysis, TGA analysis, swelling study and cell viability study. The equilibrium swelling ratio of the hydrogels has been recorded in different media and found to be at a maximum at pH 7.4. A cell viability study indicates that the hydrogel is non-cytotoxic in nature. The drug delivery results demonstrate that Dxt-g-p(HEMA) delivers ornidazole successfully in the colonic region in a controlled way and is a good candidate for an orally administered drug delivery system. The release mechanism and kinetics of ornidazole from various hydrogels have been determined using different linear and nonlinear mathematical models, which confirm that ornidazole release from hydrogel follows first order kinetics and a non-Fickian diffusion mechanism.

Synthesis and characterization of a novel polymeric hydrogel based on hydroxypropyl methyl cellulose grafted with polyacrylamide

A novel hydrogel has synthesized by grafting polyacrylamide chains onto hydroxypropyl methylcellulose in presence of potassium persulphate as initiator using solution polymerization technique. The reaction was carried out in homogeneous aqueous medium. The effect of reaction parameters on percentage of grafting (% G) and grafting efficiency (% GE) were discussed. The parameters were varied systematically to achieve the best hydrogel. Developed hydrogels were characterized by various materials characterization techniques. The dynamic and equilibrium swelling properties of hydrogels were investigated as a function of pH and time in various buffer solutions similar to that of gastric and intestinal fluid. Results showed that with increase in % G and % GE, the rate of swelling decreases, which can opens the door for further study of their utilization as matrices for controlled/sustained/targeted drug delivery.

Hydroxypropyl methyl cellulose grafted with polyacrylamide: application in controlled release of 5-amino salicylic acid.

In the present study, hydroxypropyl methyl cellulose grafted with polyacrylamide (HPMC-g-PAM) hydrogel was evaluated in vitro as a potential carrier for controlled release of 5-amino salicylic acid (5-ASA). The graft copolymer was developed by grafting PAM chains onto HPMC backbone using potassium persulphate as initiator. The swelling behaviour of hydrogel based tablet was investigated as a function of pH and time in various buffer solutions similar to that of gastric and intestinal fluids. The % equilibrium swelling was found to be higher in case of simulated intestinal fluid (pH=7.4) and lower in simulated gastric fluid (pH=1.2), making an ideal matrix as required for colon specific drug delivery. The drug release study was performed at various pH values akin to the condition of GI tract. The release kinetics of 5-ASA showed non-Fickian diffusion behaviour. This indicates that the release is controlled by a combination of polymer relaxation or erosion of the matrix and diffusion of the drug from the swollen matrix.

Development and application of a nanocomposite derived from crosslinked HPMC and Au nanoparticles for colon targeted drug delivery

Herein, we report a novel route for the synthesis of a poly(acrylamide) (PAAm) crosslinked hydroxypropyl methyl cellulose/Au nanocomposite where chemically crosslinked HPMC (c-HPMC) works as a reducing agent. At first, the crosslinked polymer was developed by grafting PAAm chains onto the HPMC backbone using ethylene glycol dimethacrylate (EGDMA) crosslinker and potassium persulfate (K2S2O8) initiator. Afterwards, AuNPs have been incorporated in situ on the surface of the crosslinked hydrogel, where the hydrogel itself reduces the tetrachloroauric acid (HAuCl4) in the reaction medium to form the nanocomposite. Different grades of nanocomposites (c-HPMC/Au) have been synthesized by altering the reaction parameters and the best one was optimized with the help of UV-visible spectroscopy. The nanocomposites synthesized, have been characterized by FTIR spectroscopy, 13C NMR spectroscopy, XRD studies, FESEM/EDAX/elemental mapping analyses, HR-TEM analysis and TGA analysis. HR-TEM analysis reveals the uniform distribution of spherical AuNPs on the surface of c-HPMC. Rheological characteristics disclose that the nanocomposite demonstrates higher gel strength than that of the crosslinked polymer, mainly because of the enhanced interactions between the organic matrix and inorganic fillers. The pH responsive behaviour of crosslinked hydrogel/composites has been confirmed by measuring the equilibrium swelling ratio in various buffer solutions (pH 1.2 and 7.4) at 37 °C. Biodegradability of the hydrogel/nanocomposite has been verified using hen egg lysozyme. The synthesized nanocomposite also demonstrates non-cytotoxic behaviour towards human mesenchymal stem cells (hMSCs). The in vitro drug release profiles indicate that both ornidazole and 5-amino salicylic acid (5-ASA) are released from the nanocomposite matrix in a controlled fashion. This confirms that the c-HPMC/Au nanocomposite is likely be an excellent alternative for the controlled release of colonic drugs. The release kinetics and mechanism of ornidazole and 5-ASA from the nanocomposite material has been explained using various linear and non-linear mathematical models.

Novel pH-responsive graft copolymer based on HPMC and poly(acrylamide) synthesised by microwave irradiation: application in controlled release of ornidazole

Herein, the microwave-assisted grafting method was employed for the development of a novel pH-responsive graft copolymer derived from polyacrylamide-modified hydroxypropyl methyl cellulose [g-HPMC (M)]. The synthesised copolymer has been used for in vitro sustained release of ornidazole. Various characterizations confirm the formation of graft copolymer. Swelling studies indicate the pH-dependent swelling behaviour, while deswelling studies suggest that g-HPMC (M) shows faster deswelling in response to change in pH and/temperature. The cell viability study signifies that g-HPMC (M) is cytocompatible. The in-vitro release study demonstrates that g-HPMC (M) delivers ornidazole specifically in the colon pH, without release of the drug in the acidic environment, ensuring g-HPMC (M) as an ideal candidate for orally administered colonic drug carriers. The kinetics and mechanism of drug release suggest that it follows a non-Fickian release mechanism.

Synthesis and characterization of biodegradable copolymer derived from dextrin and poly(vinyl acetate) via atom transfer radical polymerization

This article reports the development of a dextrin-based amphiphilic biodegradable graft copolymer (Dxt-g-pVAc) via atom transfer radical polymerization (ATRP). The copolymer was synthesized by a “grafting from” approach using 2-bromopropionyl bromide as a bromo compound, vinyl acetate as a monomer and CuBr/bpy as an activator. The monomer concentration, temperature and time were varied to obtain the copolymer (Dxt-g-pVAc) with a relatively high molecular weight (Mn) and low polydispersity index (PDI). The synthesized copolymer was well characterized using FTIR and 1H NMR spectral analyses, GPC, TGA, AFM, FESEM and EDAX analyses. The degree of substitution (DS) of dextrin was determined using 1H NMR spectroscopy. A GPC kinetics study confirmed the livingness of the ATRP of vinyl acetate on dextrin. Scanning electron microscopy (SEM) analysis showed that the copolymer has a microporous morphology, whereas an atomic force microscopy (AFM) study indicated that the roughness of the copolymer decreased after the copolymerization of poly(vinyl acetate). The gel characteristics of the copolymer were investigated using rheological parameters. A biodegradation study using hen egg lysozyme confirmed the biodegradability of the copolymer.

Modified hydroxypropyl methyl cellulose: Efficient matrix for controlled release of 5-amino salicylic acid

Hydroxypropyl methyl cellulose has been modified by grafting synthetic polyacrylamide chains [g-HPMC (M)] in presence of microwave irradiation, which has used as carrier for controlled release of 5-amino salicylic acid (5-ASA). The FTIR and UV-vis-NIR studies reveal the excellent compatibility between g-HPMC (M) and 5-ASA. Field emission scanning electron microscopy (FESEM) and UV-vis-NIR analyses suggest that physical interaction predominates between the drug and matrix. % equilibrium swelling ratio (% ESR) of g-HPMC (M) decreased with addition of salt solutions and follow the order: Na(+)>K(+)>Mg(2+)>Ca(2+)>Al(3+). The in vitro 5-ASA release studies indicate that g-HPMC (M) delivers the drug preferentially in colonic region in more sustained way than that of HPMC. The 5-ASA release follows first order kinetics and non-Fickian diffusion mechanism. These favorable features make the graft copolymer a potential matrix for colon specific delivery of 5-ASA.