Jayakrishnan A - Academia.edu (original) (raw)

Papers by Jayakrishnan A

Plasticized polyvinyl chloride (PVC), although not a blood-compatible polymer, is the material of... more Plasticized polyvinyl chloride (PVC), although not a blood-compatible polymer, is the material of choice for the manufacture of blood bags and hemodialysis tubing throughout the world. PVC is usually plasticized with di-(2-ethylhexyl phthalate) (DEHP) to impart flexibility and low temperature properties to the final product. DEHP belongs to a class of agents called hypolipidemic hepato-carcinogens, and it migrates in small quantities into the storage medium such as blood, plasma, or serum, resulting in a number of toxic effects. It has been shown that the migration resistance and blood compatibility of flexible PVC could be significantly improved by grafting polyeth-ylene glycol (PEG), the most blood-compatible polymer known today, onto the surface of flexible PVC by the classical Williamson ether synthesis reaction. The technique is simple and versatile enough to produce blood-compatible, migration resistant PVC surfaces for many medical applications. The method may also find use for preventing plas-ticizer migration from PVC cling films and polyvinylidene chloride films used extensively in food packaging. Key Words: Polyvinyl chloride—Polyethylene glycol— Grafting—Surface modification—Blood compatibility— Plasticizer migration—Di-(2-ethylhexyl phthalate).

Biomacromolecules, 2005

A naturally occurring glycosaminoglycan such as chondroitin-6-sulfate was first converted in to i... more A naturally occurring glycosaminoglycan such as chondroitin-6-sulfate was first converted in to its aldehyde derivative by periodate oxidation and used as a cross-linking agent for gelatin giving rise to a new class of hydrogels. Cross-linking was predominantly due to Schiff's base formation between the epsilon-amino groups of lysine or hydroxylysine side groups of gelatin and the aldehyde groups in oxidized chondroitin sulfate. The hydrogels were prepared from chondroitin sulfate with different degrees of oxidation and gelatin. They were characterized for degree of cross-linking, cross-linking density, equilibrium swelling, water vapor transmission rate, internal structure, and blood-compatibility. Degree of cross-linking of the gels determined by trinitrobenzene sulfonic acid assay showed that, the higher the degree of oxidation of the polysaccharide, the higher the degree of cross-linking. Examination of the internal structure by scanning electron microscopy showed that the hydrogels were highly porous in nature with interconnecting pores ranging from 50 to 200 mum. Equilibrium swelling showed that the gels retained about 90% water and did not undergo dehydration rapidly. The hydrogels were nontoxic and blood-compatible. Since an important phase of early wound healing has been shown to involve secretion of glycosaminoglycans such as chondroitin sulfate by fibroblasts which form a hydrophilic matrix suitable for remodeling during healing, this new class of hydrogels prepared from chondroitin sulfate and gelatin without employing any extraneous cross-linking agents are expected to have potential as wound dressing materials.

ABSTRACT The release profiles and anti-bacterial properties of gentamycin (GEN) incorporated into... more ABSTRACT The release profiles and anti-bacterial properties of gentamycin (GEN) incorporated into in situ forming hydrogels for application as an in situ forming wound or burn dressing was investigated. Hydrogels were prepared by mixing gentamycin (GEN) with either a solution of the oxidized alginate in 0.1 M borax or a solution of gelatin in water and combining the two solutions. The release of GEN from these gels was studied by varying the order of mixing the drug with either oxidized alginate or gelatin. The antibacterial property of these gels was evaluated using gram negative P. aeruginosa and gram positive S. aureus. The gelation reaction between periodate-oxidized alginate and gelatin through Schiff's base formation was swift enabling in situ formation of GEN-loaded hydrogels. Drug release was slow when GEN was first mixed with oxidized alginate due to conjugation of the drug to the polymer through Schiff's base while release was more rapid when it was first mixed with gelatin. Drug payload also controlled the release of drug from the hydrogel matrix. Release occurred with an initial burst effect, followed by a relatively constant release. GEN released from the hydrogels was bactericidal against both strains of bacteria used for testing

Alginate dialdehyde (ADA) biopolymers possessing a degree of oxidation of either 10 or 50% (10-AD... more Alginate dialdehyde (ADA) biopolymers possessing a degree of oxidation of either 10 or 50% (10-ADA and 50-ADA, respectively) were characterized using FTIR, XPS and SEC. The aldehyde vibrational mode at 1740 cm À1 was observed only in ADA which had been equilibrated under ambient conditions while dry samples did not display this band. Spectral changes, both FTIR and XPS, were consistent with formation of hemiacetal moieties. The two types of ADA (10-ADA and 50-ADA) were used as macromolecular crosslinkers to form labile covalent crosslinks in alginate hydrogels. The compositions and properties of the hydrogels were explored through measurement of water uptake and stability in aqueous solution, and characterising the internal structure and mechanical properties by cryogenic scanning electron microscopy and tensile testing, respectively. A decrease in water content was observed when using 50-ADA as compared to 10-ADA correlating with a higher number of crosslinks formed in the hydrogel incorporating 50-ADA. Water uptake also correlated with the amount of 50-ADA incorporated. All ADA–alginate hydrogels displayed short term stability of 3 days after immersion in aqueous solution. The stability of the 50-ADA containing hydrogel was enhanced by introducing ionic crosslinking. Tensile properties of the hydrogels were found to be dependent on the overall polymer density and uniformity of the crosslinking.

Vascular grafts are devices intended to replace compromised arteries in the body and grafts made ... more Vascular grafts are devices intended to replace compromised arteries in the body and grafts made of poly-ethylene terephthalate (PET) fabric have been used mainly for synthetic grafting procedures involving medium to large diameter vascular grafts. Though porosity of the graft permits tissue in-growth, it would lead to bleeding through the graft walls immediately after implantation. So it is essential to seal the pores either by preclotting with patient's own blood or by other sealing materials prior to implantation in order to prevent blood leakage through the graft wall. Biodegradable hydrogel materials are ideal candidates for this purpose. Apart from sealing the pores, they offer biocompatible and low-thrombogenic surfaces when coated on vascular graft. In the present study, a biodegradable hydrogel, derived from oxidized alginate and gelatin, has been deposited on PET grafts by dip coating and were characterized for its efficacy on sealing the pores of the graft. Water permeability in the static and pulsatile conditions, burst strength, in vitro cell culture cytotoxicity, hemocompatibility, and endothelial cell adhesion and proliferation of the coated grafts were investigated. Results showed that the alginate dialdehyde cross-linked gelatin hydrogel was nontoxic, hemocompatible, and was efficient in sealing the pores of the graft. Blood perfu-sion study showed that when hydrogel-coated grafts were exposed to blood for 30 min, they showed little affinity toward platelets or leukocytes. Hemolytic potential of PET was significantly reduced when it was coated with hydrogel. Improved adhesion and proliferation of endothelial cells were observed when PET grafts were coated with hydrogel. Results also showed that coating with hydrogel did not affect the burst strength of the PET graft. V C 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 98B: 139– 149, 2011.

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for ... more The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture.

A method for the preparation of smooth, spherical, glutaraldehyde-crosslinked microspheres of the... more A method for the preparation of smooth, spherical, glutaraldehyde-crosslinked microspheres of the amphiphilic protein, casein, is reported. Casein microspheres (CAS/MS) were found to be even more hydrophilic than comparable microspheres made from bovine serum albumin by the method developed in this laboratory several years ago and were readily dispersed in water without aggregation. Enzymatic degradation studies with the enzyme protease suggested that the CAS/MS with lower crosslink density degraded faster than those with higher crosslink density. Methotrexate (MTX) was incorporated into the CAS/MS during microsphere synthesis to the extent of 15 wt% loading, and in vitro release was examined in phosphate buffer at 37°C. Drug release of 35% was observed in 24 h, suggesting that most of the incorporated drug was strongly associated with the CAS/MS. Similar release was observed for MTX loaded albumin spheres prepared in the same manner. Based on these studies, casein appears to be a highly promising, low-cost, bioacceptable protein for the synthesis of drug conjugates and microsphere carrier systems for targeted drug delivery.

xhitosan microspheres having good spherical geometry and a smooth surface were prepared by the gl... more xhitosan microspheres having good spherical geometry and a smooth surface were prepared by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilizing agent. Microspheres having different degrees of swelling were made by varying the cross-linking density. Microspheres were prepared by incorporating theophylline, aspirin or griseofulvin. Drug incorporation efficiencies exceeding 80% could be achieved for these drugs. In-vitro release studies of these drugs were carried out in simulated gastric and intestinal fluids at 37°C. It was observed that the drug release rates were influenced by the cross-linking density, particle size and initial drug loading in the microspheres.

Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulato... more Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. To explore more effective wound management, dibutyryl cyclic adenosine monophosphate (DBcAMP), a lipophilic analog of cAMP was incorporated into an in situ-forming hydrogel wound dressing based on periodate-oxidized alginate and gelatin. In vitro release of DBcAMP from the matrix into phosphate buffered saline was slow and increased with time. Only 50–60% of the compound was released into the medium over a period of 2 days suggestive of a sustained release into the wound bed over a period of few days. The wound-healing efficacy of the DBcAMP-incorporated dressing was evaluated on experimental full-thickness wounds in a rat model. It was found that dressing promoted wound healing leading to complete re-epithelialization of wounds within 10 days, whereas control wounds took 15 days for complete re-epithelialization. Data obtained in this study showed that the presence of DBcAMP accelerated healing and re-epithelialization of full-thickness wounds.

Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched polysaccharide, to fo... more Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched polysaccharide, to form the imino conjugate of the drug and the polysaccharide. The water-soluble conjugate was dispersed by sonication in a mixture of toluene and liquid paraffin in the presence of a non-ionic surfactant as droplet stabilizer and fabricated into microspheres by heat denaturation at 80°C to obtain spheres less than 2 mm in diameter. These microspheres did not undergo dissolution in water on prolonged incubation. In-vitro release of ampicillin into phosphate buffer from the microspheres was slow and sustained with a cumulative release between 10 and 25% of the drug content in 10 days depending on the degree of oxidation of GA and the drug payload. Release into simulated gastric fluid was faster due to faster hydrolysis of the drug–GA bond in the acid medium, but when the medium was changed to intestinal fluid, the release was slowed down. Ampicillin released was functionally active and inhibited the growth of S. aureus and E. coli in cultures, although not as actively as free ampicillin. The microspheres underwent slow biodegradation on prolonged incubation in aqueous media. These studies show that ampicillin conjugated with oxidized GA and fabricated into microspheres possesses sustained-release characteristics for prolonged periods.

The synthesis and characterization of polyurethane (PU) with excellent radiopacity for medical an... more The synthesis and characterization of polyurethane (PU) with excellent radiopacity for medical and allied applications are reported. Bisphenol-A (BPA) was iodinated to obtain 4,4 0-isopropylidinedi-(2,6-diiodo-phenol) (IBPA) which was used as a chain extender for the preparation of a radiopaque PU. The PU was prepared by reacting 4,4 0-methylenebis(phenyl isocyanate) (MDI), poly(tetramethylene glycol) (PTMG) and IBPA in 2.2:1.2:1 molecular ratio and is characterized by infrared spectroscopy (IR), thermog-ravimetry (TGA), dynamic mechanical analysis (DMA), energy dispersive X-ray analysis (EDX), gel permeation chromatography (GPC) and X-radiography. X-ray images showed that the PU prepared using IBPA as the chain extender is highly radiopaque. An in vitro cytotoxicity test using L929 mouse fibroblast cells shows that the PU is non-cytotoxic. The outlined synthesis of a PU with radiocontrast properties opens up the possibility of synthesizing many different kinds of radiopaque PUs with desirable range of physical properties exploiting the versatility in their chemical synthesis.

The kinetics of polymerization of acrylonitrile initiated by the redox systems cyanoacetic acid/M... more The kinetics of polymerization of acrylonitrile initiated by the redox systems cyanoacetic acid/Mn(OAc)3 and cyanoacetic acid/tris(benzoylacetonato)manganese(llI) in dimethylsulphoxide as solvent have been investigated over the range 20-35L The kinetics of oxidation are consistent with the formation of intermediate complexes between the reactants, followed by electron transfer. Manganous ions inhibit the reaction by competitive complexation. The primary radicals are very efficient as initiators of polymerization which is terminated by mutual interaction of macroradicals. Mechanisms have been proposed to explain the kinetics; rate and equilibrium constants have been evaluated.

A new class of radiopaque copolymer using methyl methacrylate (MMA) and glycidyl methacrylate (GM... more A new class of radiopaque copolymer using methyl methacrylate (MMA) and glycidyl methacrylate (GMA) monomers was synthesized and characterized. The copolymer was made radiopaque by the epoxide ring opening of GMA using the catalyst o-phenylenediamine and the subsequent covalent attachment of elemental iodine. The copolymer was characterized by Fourier transform infrared (FTIR) spectra, energy dispersive X-ray analysis using environmental scanning electron microscope (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). X-ray visibility of the copolymer was checked by X-radiography. Blood compatibility and cytotoxicity of the newly synthesized copolymer were also evaluated. The iodinated copolymer was thermally stable, blood compatible, non-cytotoxic, and highly radiopaque. The presence of bulky iodine group created a new copolymer with modified properties for potential use in biomedical applications.

A new iodine-containing methacrylate mono-mer, 3,4,5-triiodobenzoyloxyethyl methacrylate (TIBEM),... more A new iodine-containing methacrylate mono-mer, 3,4,5-triiodobenzoyloxyethyl methacrylate (TIBEM), was synthesized by coupling 2-hydroxyethyl methacrylate (HEMA) with 3,4,5-triiodobenzoic acid. The monomer was characterized by 1 H nuclear magnetic resonance, infrared (IR), and ultraviolet spectra. Homopolymerization and copolymeriza-tion of the monomer with methyl methacrylate (MMA) were carried out using 2,2-azobis isobutyronitrile as the initiator. A terpolymer of TIBEM, MMA, and HEMA was also synthesized. The copolymers were characterized by IR, gel per-meation chromatography, differential thermal analysis, and thermogravimetric analysis (TGA). High molecular weight polymers were produced with MMA at different feed compositions of TIBEM. The polymers were found to be freely soluble in common solvents for acrylic polymers. TGA showed little decomposition of the copolymer below 280°C. Copolymers showed good radiopacity at 25 wt % of TIBEM in the feed. These copolymers could find applications in medical and dental areas where radiopacity is a desirable feature of the implants.

Plasticized poly(vinyl chloride) (PVC) sheets were surface modified by nucleophilic substitution ... more Plasticized poly(vinyl chloride) (PVC) sheets were surface modified by nucleophilic substitution of chlorine by azide in aqueous media under phase transfer conditions. PVC was reacted with a 40% solution of sodium azide in water using tetrabutyl ammonium bromide as the phase transfer catalyst. The reaction was conducted at temperatures ranging from 50 to 80°C for various periods of time (1-4 h). The azidated PVC surface was then irradiated using u.v. light with a 125 W lamp for various time periods to crosslink the surface. Migration of the plasticizer di-(2-ethylhexyl phthalate) from surface modified and unmodified PVC was examined in a potential organic extractant such as hexane. It was found that considerable reduction in the migration of the plasticizer could be achieved by this technique depending on the extent of azidation of the PVC surface and the irradiation dose. Determination of the stress/strain properties of PVC sheets before and after modification showed that there was around 30% reduction in these properties after surface modification. However, the values were still much above the minimum prescribed for vinyl chloride polymers used in biomedical applications. (Keywords: poly(vinyl chloride); di-(2-ethylhexyl phthalate); plasticizer migration) INTRODUCTION The migration of phthalate esters, which are commonly employed as plasticizers for imparting flexibility and low temperature properties to poly(vinyl chloride) (PVC), has been a subject of concern in PVC based medical devices 1-5. Plasticized PVC used in sheet and tubular forms in medical devices contains up to 40% by weight of the plasticizer, usually di-(2-ethylhexyl phthalate) (DEHP) °. Various attempts have been made to reduce the migration of this plasticizer from PVC used in medical , pharmaceutical and food packaging applications. Techniques employed include coating the surface of PVC using various polymers such as acrylates, polyesters or polyurethanes, cross-linking the PVC during processing using peroxides or by radiation in the presence of multifunctional monomers, and grafting hydrophilic monomers onto the surface using gamma radiation 7-1°. PVC reacts with sodium azide in solvents such as dimethyl formamide, dimethyl sulfoxide or hexamethyl-phosphortriamide in the absence of a catalyst to yield the polymeric azide 11. In a recent study, we have demonstrated that coating azidated PVC onto plasticized PVC sheets and photocrosslinking the coatings retard the plasticizer migration significantly 12. A 50-80% reduction in migration could be achieved in potential organic solvents such as hexane depending on the concentration of the coating solution, coating thickness and irradiation dose. If the azidation reaction could be conducted

Plasticized polyvinyl chloride (PVC), although not a blood-compatible polymer, is the material of... more Plasticized polyvinyl chloride (PVC), although not a blood-compatible polymer, is the material of choice for the manufacture of blood bags and hemodialysis tubing throughout the world. PVC is usually plasticized with di-(2-ethylhexyl phthalate) (DEHP) to impart flexibility and low temperature properties to the final product. DEHP belongs to a class of agents called hypolipidemic hepato-carcinogens, and it migrates in small quantities into the storage medium such as blood, plasma, or serum, resulting in a number of toxic effects. It has been shown that the migration resistance and blood compatibility of flexible PVC could be significantly improved by grafting polyeth-ylene glycol (PEG), the most blood-compatible polymer known today, onto the surface of flexible PVC by the classical Williamson ether synthesis reaction. The technique is simple and versatile enough to produce blood-compatible, migration resistant PVC surfaces for many medical applications. The method may also find use for preventing plas-ticizer migration from PVC cling films and polyvinylidene chloride films used extensively in food packaging. Key Words: Polyvinyl chloride—Polyethylene glycol— Grafting—Surface modification—Blood compatibility— Plasticizer migration—Di-(2-ethylhexyl phthalate).

Biomacromolecules, 2005

A naturally occurring glycosaminoglycan such as chondroitin-6-sulfate was first converted in to i... more A naturally occurring glycosaminoglycan such as chondroitin-6-sulfate was first converted in to its aldehyde derivative by periodate oxidation and used as a cross-linking agent for gelatin giving rise to a new class of hydrogels. Cross-linking was predominantly due to Schiff's base formation between the epsilon-amino groups of lysine or hydroxylysine side groups of gelatin and the aldehyde groups in oxidized chondroitin sulfate. The hydrogels were prepared from chondroitin sulfate with different degrees of oxidation and gelatin. They were characterized for degree of cross-linking, cross-linking density, equilibrium swelling, water vapor transmission rate, internal structure, and blood-compatibility. Degree of cross-linking of the gels determined by trinitrobenzene sulfonic acid assay showed that, the higher the degree of oxidation of the polysaccharide, the higher the degree of cross-linking. Examination of the internal structure by scanning electron microscopy showed that the hydrogels were highly porous in nature with interconnecting pores ranging from 50 to 200 mum. Equilibrium swelling showed that the gels retained about 90% water and did not undergo dehydration rapidly. The hydrogels were nontoxic and blood-compatible. Since an important phase of early wound healing has been shown to involve secretion of glycosaminoglycans such as chondroitin sulfate by fibroblasts which form a hydrophilic matrix suitable for remodeling during healing, this new class of hydrogels prepared from chondroitin sulfate and gelatin without employing any extraneous cross-linking agents are expected to have potential as wound dressing materials.

ABSTRACT The release profiles and anti-bacterial properties of gentamycin (GEN) incorporated into... more ABSTRACT The release profiles and anti-bacterial properties of gentamycin (GEN) incorporated into in situ forming hydrogels for application as an in situ forming wound or burn dressing was investigated. Hydrogels were prepared by mixing gentamycin (GEN) with either a solution of the oxidized alginate in 0.1 M borax or a solution of gelatin in water and combining the two solutions. The release of GEN from these gels was studied by varying the order of mixing the drug with either oxidized alginate or gelatin. The antibacterial property of these gels was evaluated using gram negative P. aeruginosa and gram positive S. aureus. The gelation reaction between periodate-oxidized alginate and gelatin through Schiff's base formation was swift enabling in situ formation of GEN-loaded hydrogels. Drug release was slow when GEN was first mixed with oxidized alginate due to conjugation of the drug to the polymer through Schiff's base while release was more rapid when it was first mixed with gelatin. Drug payload also controlled the release of drug from the hydrogel matrix. Release occurred with an initial burst effect, followed by a relatively constant release. GEN released from the hydrogels was bactericidal against both strains of bacteria used for testing

Alginate dialdehyde (ADA) biopolymers possessing a degree of oxidation of either 10 or 50% (10-AD... more Alginate dialdehyde (ADA) biopolymers possessing a degree of oxidation of either 10 or 50% (10-ADA and 50-ADA, respectively) were characterized using FTIR, XPS and SEC. The aldehyde vibrational mode at 1740 cm À1 was observed only in ADA which had been equilibrated under ambient conditions while dry samples did not display this band. Spectral changes, both FTIR and XPS, were consistent with formation of hemiacetal moieties. The two types of ADA (10-ADA and 50-ADA) were used as macromolecular crosslinkers to form labile covalent crosslinks in alginate hydrogels. The compositions and properties of the hydrogels were explored through measurement of water uptake and stability in aqueous solution, and characterising the internal structure and mechanical properties by cryogenic scanning electron microscopy and tensile testing, respectively. A decrease in water content was observed when using 50-ADA as compared to 10-ADA correlating with a higher number of crosslinks formed in the hydrogel incorporating 50-ADA. Water uptake also correlated with the amount of 50-ADA incorporated. All ADA–alginate hydrogels displayed short term stability of 3 days after immersion in aqueous solution. The stability of the 50-ADA containing hydrogel was enhanced by introducing ionic crosslinking. Tensile properties of the hydrogels were found to be dependent on the overall polymer density and uniformity of the crosslinking.

Vascular grafts are devices intended to replace compromised arteries in the body and grafts made ... more Vascular grafts are devices intended to replace compromised arteries in the body and grafts made of poly-ethylene terephthalate (PET) fabric have been used mainly for synthetic grafting procedures involving medium to large diameter vascular grafts. Though porosity of the graft permits tissue in-growth, it would lead to bleeding through the graft walls immediately after implantation. So it is essential to seal the pores either by preclotting with patient's own blood or by other sealing materials prior to implantation in order to prevent blood leakage through the graft wall. Biodegradable hydrogel materials are ideal candidates for this purpose. Apart from sealing the pores, they offer biocompatible and low-thrombogenic surfaces when coated on vascular graft. In the present study, a biodegradable hydrogel, derived from oxidized alginate and gelatin, has been deposited on PET grafts by dip coating and were characterized for its efficacy on sealing the pores of the graft. Water permeability in the static and pulsatile conditions, burst strength, in vitro cell culture cytotoxicity, hemocompatibility, and endothelial cell adhesion and proliferation of the coated grafts were investigated. Results showed that the alginate dialdehyde cross-linked gelatin hydrogel was nontoxic, hemocompatible, and was efficient in sealing the pores of the graft. Blood perfu-sion study showed that when hydrogel-coated grafts were exposed to blood for 30 min, they showed little affinity toward platelets or leukocytes. Hemolytic potential of PET was significantly reduced when it was coated with hydrogel. Improved adhesion and proliferation of endothelial cells were observed when PET grafts were coated with hydrogel. Results also showed that coating with hydrogel did not affect the burst strength of the PET graft. V C 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 98B: 139– 149, 2011.

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for ... more The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture.

A method for the preparation of smooth, spherical, glutaraldehyde-crosslinked microspheres of the... more A method for the preparation of smooth, spherical, glutaraldehyde-crosslinked microspheres of the amphiphilic protein, casein, is reported. Casein microspheres (CAS/MS) were found to be even more hydrophilic than comparable microspheres made from bovine serum albumin by the method developed in this laboratory several years ago and were readily dispersed in water without aggregation. Enzymatic degradation studies with the enzyme protease suggested that the CAS/MS with lower crosslink density degraded faster than those with higher crosslink density. Methotrexate (MTX) was incorporated into the CAS/MS during microsphere synthesis to the extent of 15 wt% loading, and in vitro release was examined in phosphate buffer at 37°C. Drug release of 35% was observed in 24 h, suggesting that most of the incorporated drug was strongly associated with the CAS/MS. Similar release was observed for MTX loaded albumin spheres prepared in the same manner. Based on these studies, casein appears to be a highly promising, low-cost, bioacceptable protein for the synthesis of drug conjugates and microsphere carrier systems for targeted drug delivery.

xhitosan microspheres having good spherical geometry and a smooth surface were prepared by the gl... more xhitosan microspheres having good spherical geometry and a smooth surface were prepared by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilizing agent. Microspheres having different degrees of swelling were made by varying the cross-linking density. Microspheres were prepared by incorporating theophylline, aspirin or griseofulvin. Drug incorporation efficiencies exceeding 80% could be achieved for these drugs. In-vitro release studies of these drugs were carried out in simulated gastric and intestinal fluids at 37°C. It was observed that the drug release rates were influenced by the cross-linking density, particle size and initial drug loading in the microspheres.

Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulato... more Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. To explore more effective wound management, dibutyryl cyclic adenosine monophosphate (DBcAMP), a lipophilic analog of cAMP was incorporated into an in situ-forming hydrogel wound dressing based on periodate-oxidized alginate and gelatin. In vitro release of DBcAMP from the matrix into phosphate buffered saline was slow and increased with time. Only 50–60% of the compound was released into the medium over a period of 2 days suggestive of a sustained release into the wound bed over a period of few days. The wound-healing efficacy of the DBcAMP-incorporated dressing was evaluated on experimental full-thickness wounds in a rat model. It was found that dressing promoted wound healing leading to complete re-epithelialization of wounds within 10 days, whereas control wounds took 15 days for complete re-epithelialization. Data obtained in this study showed that the presence of DBcAMP accelerated healing and re-epithelialization of full-thickness wounds.

Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched polysaccharide, to fo... more Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched polysaccharide, to form the imino conjugate of the drug and the polysaccharide. The water-soluble conjugate was dispersed by sonication in a mixture of toluene and liquid paraffin in the presence of a non-ionic surfactant as droplet stabilizer and fabricated into microspheres by heat denaturation at 80°C to obtain spheres less than 2 mm in diameter. These microspheres did not undergo dissolution in water on prolonged incubation. In-vitro release of ampicillin into phosphate buffer from the microspheres was slow and sustained with a cumulative release between 10 and 25% of the drug content in 10 days depending on the degree of oxidation of GA and the drug payload. Release into simulated gastric fluid was faster due to faster hydrolysis of the drug–GA bond in the acid medium, but when the medium was changed to intestinal fluid, the release was slowed down. Ampicillin released was functionally active and inhibited the growth of S. aureus and E. coli in cultures, although not as actively as free ampicillin. The microspheres underwent slow biodegradation on prolonged incubation in aqueous media. These studies show that ampicillin conjugated with oxidized GA and fabricated into microspheres possesses sustained-release characteristics for prolonged periods.

The synthesis and characterization of polyurethane (PU) with excellent radiopacity for medical an... more The synthesis and characterization of polyurethane (PU) with excellent radiopacity for medical and allied applications are reported. Bisphenol-A (BPA) was iodinated to obtain 4,4 0-isopropylidinedi-(2,6-diiodo-phenol) (IBPA) which was used as a chain extender for the preparation of a radiopaque PU. The PU was prepared by reacting 4,4 0-methylenebis(phenyl isocyanate) (MDI), poly(tetramethylene glycol) (PTMG) and IBPA in 2.2:1.2:1 molecular ratio and is characterized by infrared spectroscopy (IR), thermog-ravimetry (TGA), dynamic mechanical analysis (DMA), energy dispersive X-ray analysis (EDX), gel permeation chromatography (GPC) and X-radiography. X-ray images showed that the PU prepared using IBPA as the chain extender is highly radiopaque. An in vitro cytotoxicity test using L929 mouse fibroblast cells shows that the PU is non-cytotoxic. The outlined synthesis of a PU with radiocontrast properties opens up the possibility of synthesizing many different kinds of radiopaque PUs with desirable range of physical properties exploiting the versatility in their chemical synthesis.

The kinetics of polymerization of acrylonitrile initiated by the redox systems cyanoacetic acid/M... more The kinetics of polymerization of acrylonitrile initiated by the redox systems cyanoacetic acid/Mn(OAc)3 and cyanoacetic acid/tris(benzoylacetonato)manganese(llI) in dimethylsulphoxide as solvent have been investigated over the range 20-35L The kinetics of oxidation are consistent with the formation of intermediate complexes between the reactants, followed by electron transfer. Manganous ions inhibit the reaction by competitive complexation. The primary radicals are very efficient as initiators of polymerization which is terminated by mutual interaction of macroradicals. Mechanisms have been proposed to explain the kinetics; rate and equilibrium constants have been evaluated.

A new class of radiopaque copolymer using methyl methacrylate (MMA) and glycidyl methacrylate (GM... more A new class of radiopaque copolymer using methyl methacrylate (MMA) and glycidyl methacrylate (GMA) monomers was synthesized and characterized. The copolymer was made radiopaque by the epoxide ring opening of GMA using the catalyst o-phenylenediamine and the subsequent covalent attachment of elemental iodine. The copolymer was characterized by Fourier transform infrared (FTIR) spectra, energy dispersive X-ray analysis using environmental scanning electron microscope (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). X-ray visibility of the copolymer was checked by X-radiography. Blood compatibility and cytotoxicity of the newly synthesized copolymer were also evaluated. The iodinated copolymer was thermally stable, blood compatible, non-cytotoxic, and highly radiopaque. The presence of bulky iodine group created a new copolymer with modified properties for potential use in biomedical applications.

A new iodine-containing methacrylate mono-mer, 3,4,5-triiodobenzoyloxyethyl methacrylate (TIBEM),... more A new iodine-containing methacrylate mono-mer, 3,4,5-triiodobenzoyloxyethyl methacrylate (TIBEM), was synthesized by coupling 2-hydroxyethyl methacrylate (HEMA) with 3,4,5-triiodobenzoic acid. The monomer was characterized by 1 H nuclear magnetic resonance, infrared (IR), and ultraviolet spectra. Homopolymerization and copolymeriza-tion of the monomer with methyl methacrylate (MMA) were carried out using 2,2-azobis isobutyronitrile as the initiator. A terpolymer of TIBEM, MMA, and HEMA was also synthesized. The copolymers were characterized by IR, gel per-meation chromatography, differential thermal analysis, and thermogravimetric analysis (TGA). High molecular weight polymers were produced with MMA at different feed compositions of TIBEM. The polymers were found to be freely soluble in common solvents for acrylic polymers. TGA showed little decomposition of the copolymer below 280°C. Copolymers showed good radiopacity at 25 wt % of TIBEM in the feed. These copolymers could find applications in medical and dental areas where radiopacity is a desirable feature of the implants.

Plasticized poly(vinyl chloride) (PVC) sheets were surface modified by nucleophilic substitution ... more Plasticized poly(vinyl chloride) (PVC) sheets were surface modified by nucleophilic substitution of chlorine by azide in aqueous media under phase transfer conditions. PVC was reacted with a 40% solution of sodium azide in water using tetrabutyl ammonium bromide as the phase transfer catalyst. The reaction was conducted at temperatures ranging from 50 to 80°C for various periods of time (1-4 h). The azidated PVC surface was then irradiated using u.v. light with a 125 W lamp for various time periods to crosslink the surface. Migration of the plasticizer di-(2-ethylhexyl phthalate) from surface modified and unmodified PVC was examined in a potential organic extractant such as hexane. It was found that considerable reduction in the migration of the plasticizer could be achieved by this technique depending on the extent of azidation of the PVC surface and the irradiation dose. Determination of the stress/strain properties of PVC sheets before and after modification showed that there was around 30% reduction in these properties after surface modification. However, the values were still much above the minimum prescribed for vinyl chloride polymers used in biomedical applications. (Keywords: poly(vinyl chloride); di-(2-ethylhexyl phthalate); plasticizer migration) INTRODUCTION The migration of phthalate esters, which are commonly employed as plasticizers for imparting flexibility and low temperature properties to poly(vinyl chloride) (PVC), has been a subject of concern in PVC based medical devices 1-5. Plasticized PVC used in sheet and tubular forms in medical devices contains up to 40% by weight of the plasticizer, usually di-(2-ethylhexyl phthalate) (DEHP) °. Various attempts have been made to reduce the migration of this plasticizer from PVC used in medical , pharmaceutical and food packaging applications. Techniques employed include coating the surface of PVC using various polymers such as acrylates, polyesters or polyurethanes, cross-linking the PVC during processing using peroxides or by radiation in the presence of multifunctional monomers, and grafting hydrophilic monomers onto the surface using gamma radiation 7-1°. PVC reacts with sodium azide in solvents such as dimethyl formamide, dimethyl sulfoxide or hexamethyl-phosphortriamide in the absence of a catalyst to yield the polymeric azide 11. In a recent study, we have demonstrated that coating azidated PVC onto plasticized PVC sheets and photocrosslinking the coatings retard the plasticizer migration significantly 12. A 50-80% reduction in migration could be achieved in potential organic solvents such as hexane depending on the concentration of the coating solution, coating thickness and irradiation dose. If the azidation reaction could be conducted