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Biomedical subjects

A Jayakrishnan

Publications and source records attributed to A Jayakrishnan.

47 records · Page 3Linked to original sources

Suspension polymerization of 2-hydroxyethyl methacrylate in the presence of polymeric diluents: a novel route to spherical highly porous beads for biomedical applications.

Spherical, highly porous beads of poly(2-hydroxyethyl methacrylate) (PHEMA) cross-linked with ethylene glycol dimethacrylate (EGDM) were prepared by suspension polymerization of HEMA in concentrated NaCl solutions in presence of toluene, poly(methyl methacrylate) (PMMA) in toluene, and poly(tetramethylene glycol) (PTMG). Magnesium hydroxide prepared in situ in the dispersion medium gave the best stabilization effect for the monomer droplets. In the presence of PTMG, beads having nearly 1.0 mm in diameter could be prepared, while toluene alone as the diluent produced beads of very small size. Removal of PMMA or PTMG from the beads after polymerization using suitable solvents gave rise to highly porous PHEMA microspsheres. Polymerization in the presence of PTMG produced microspsheres with better spherical geometry as compared to those generated in the presence of PMMA. The effect of various factors such as NaCl concentration, concentration of Mg(OH)2, and the concentration of PMMA or PTMG in the monomer phase on the stability of the suspension and the particle size distribution was investigated.

Cross-Linking Reagents↗

Preparation and evaluation of radiopaque hydrogel microspheres based on PHEMA/iothalamic acid and PHEMA/iopanoic acid as particulate emboli.

Highly porous poly(2-hydroxyethyl methacrylate) (PHEMA) microspheres prepared by suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) in presence of polymeric diluents such as poly(methyl methacrylate) (PMMA) in toluene and poly(tetramethylene glycol) (PTMG) were made radiopaque by esterification of the reactive hydroxyl groups with iothalamic acid and iopanoic acid, two radiopaque substances clinically used. Of the various solvents and catalysts examined, tetrahydrofuran (THF) and N,N'-dimethyl paratoluidine (DMPT) were found to be best for obtaining a high degree of conversion. More than 30 wt% iodine could be bound to the microspheres which made them sufficiently radiopaque to be imaged radiographically. Microspheres retained their porosity, swelling ability, hydrophilicity, and surface morphology to a significant extent after iodination. Preliminary implantation studies of such microspheres subcutaneously in rats have shown no adverse tissue reactions over a 6-month period. It is suggested that these microspheres would prove to be useful as particulate emboli in endovascular embolization.

Animals↗

Barium sulphate-loaded p(HEMA) microspheres as artificial emboli: preparation and properties.

Poly(2-hydroxyethyl methacrylate) p(HEMA) microspheres of good spherical geometry (diameter 90-1500 microns) encapsulated with 40-50% barium sulphate to impart radiopaque properties were prepared by a solvent evaporation process. These microspheres were cross-linked by reacting with hexamethylene diisocyanate (HMDI) or by gamma-irradiation in the presence of ethylene glycol dimethacrylate (EGDM) in n-heptane. Microspheres with a porous structure and a rough surface were also made by the incorporation of NaCl along with BaSO4. The effects of concentration of the polymer solution, concentration of the stabilizing agent, concentration of BaSO4, viscosity of the dispersion medium and ratio of the dispersed phase to the dispersion medium on the formation, stability and particle size distribution of the microspheres were investigated.

Barium Sulfate↗

Synthetic hydrogel microspheres as substrata for cell adhesion and growth.

Cross-linked poly(methyl methacrylate) (PMMA) microspheres were subjected to alkaline hydrolysis to obtain hydrophilic microspheres having carboxyl residues distributed throughout the matrix. These microspheres were found to support the growth of human skin fibroblasts and human heart and lung cells. Further, fibroblasts grown on them were found to be comparable with those grown on the commercial tissue culture plate with respect to [14C]amino acid uptake and incorporation into proteins. The hydrolyzed PMMA microspheres may find application as a microcarrier for cell culture.

Cell Adhesion↗

Preparation and in vitro evaluation of primaquine-conjugated gum arabic microspheres.

Gum arabic, a branched polysaccharide, was oxidized using periodate to generate reactive aldehyde groups on the biopolymer. Primaquine, an 8-aminoquinoline, was covalently coupled onto oxidized gum arabic via an imine bond and simultaneously fabricated into microspheres of less than 2 microm in size by heat denaturation in a reverse emulsion of 1:1 light paraffin oil and toluene stabilized by sorbitan sesquioleate as the surfactant. The covalent binding of primaquine to the polysaccharide using the clinically used water-soluble form of the drug primaquine phosphate was achieved in the presence of borate buffer of pH 11. Up to 35% of the drug could be bound to the polymer backbone depending on the concentration of the drug employed initially and the degree of oxidation of the polysaccharide. Interestingly, both the aliphatic and the hindered aromatic amino groups of primaquine were found to react with the aldehyde functions through Schiff base formation leading to cross-linking of the polysaccharide with the drug itself. In vitro release of the drug from microspheres into phosphate buffered saline (PBS, pH 7.4, 0.1 M) at 37 degrees C showed that the release of primaquine from the matrix was slow, although gradually increased with time. The maximum released was below 50% of the drug payload even after 10 days. Release into simulated gastric and intestinal fluids was faster compared to the release in PBS due to rapid hydrolysis of the Schiff's linkage in the gastric fluid. A possible reason for the poor hydrolytic susceptibility of the Schiff's linkage is suggested based on the unequal reactivity of the amino groups on primaquine and its relevance in possible therapeutic application of this polymer-drug conjugate discussed.

Antimalarials↗

Oxidized chondroitin sulfate-cross-linked gelatin matrixes: a new class of hydrogels.

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.

Cells, Cultured↗

Radiopaque hydrogel microspheres.

Spherical, hydrophilic microspheres prepared from crosslinked poly(methyl methacrylate) (PMMA) by alkaline hydrolysis have been made radiopaque by impregnating with barium sulphate by the precipitation technique. Microspheres having carboxyl functions as their alkali metal salt were swollen in sodium sulphate solution and barium sulphate entrapment was effected by treating with barium chloride solution. The swelling characteristics of the microspheres could be controlled by acidification and further by anhydride formation thereby trapping the barium sulphate firmly inside the microspheres. Barium sulphate loading of up to 70 wt-per cent could be achieved by this technique. These microspheres have been found to possess excellent X-ray contrast properties and may find application as particulate emboli in endovascular embolization.

Barium Sulfate↗

Tantalum loaded silicone microspheres as particulate emboli.

Chloroform solutions of medical grade silicone resin were cured in an aqueous dispersion medium containing poly(vinyl alcohol) (PVA) as the drop stabilizer at 40-60 degrees C to generate smooth, spherical, elastic microspheres. The microspheres were encapsulated with tantalum powder to render them radiopaque. Tantalum loaded microspheres having diameter more than 1.00 mm could be prepared by this technique. Incorporation of radiopaques such as barium sulphate and methyl iothalamate resulted in the instability of the suspension giving rise to an agglomerated product. Microspheres were grafted with hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) and N-vinyl pyrrolidone (NVP) using ionizing radiation from a 60Co source in an effort to make their surfaces hydrophilic. While the graft yield was very little when HEMA alone was used for grafting, a combination of HEMA/NVP in a 1:1 ratio produced better graft yields resulting in improved surface hydrophilicity. The tantalum loaded microspheres were found to be very resistant to surface modification. Microspheres could be dispersed in water with the aid of small quantities of surfactants such as Tween 20. These microspheres may find use in particulate embolization.

Chemical Phenomena↗

Evaluation of an aliphatic polyurethane as a microsphere matrix for sustained theophylline delivery.

In spite of several biomedical applications of polyurethanes, very little attention has been focused on these polymers for controlled drug delivery. In this study, an aliphatic polyurethane, Tecoflex, was evaluated as a microsphere matrix for the controlled release of theophylline. Polyurethane microspheres containing theophylline were prepared using a solvent evaporation technique from a dichloromethane solution of the polymer containing the drug. A dilute solution of poly(vinyl alcohol) served as the dispersion medium. Microspheres of good spherical geometry having theophylline content of 35% could be prepared by the technique. The release of the drug from the microspheres was examined in simulated gastric and intestinal fluids at 37 degrees C. While a large burst effect was observed in gastric fluid, in the intestinal fluid a close to zero-order release was seen. Attempts were made to modulate the release by incorporating poly(ethylene glycol) in the matrix and also coating the spheres with paraffin wax. Preliminary data indicate that polyurethanes could be interesting matrices for controlled drug delivery.

Chemistry, Pharmaceutical↗

A new method for the synthesis of smooth, round, hydrophilic protein microspheres using low concentrations of polymeric dispersing agents.

A new method for the synthesis of protein microspheres of wide size range having good spherical geometry and hydrophilicity using very low concentrations of polymeric dispersing agents is reported. The method involves the use of around 1% solution of a biomedical grade aliphatic polyurethane in a mixture of a hexane and dichloromethane as the dispersion medium, as opposed to a 25-30% solution of polymeric dispersing agents employed by previous workers to effect steric stabilization of the protein solution droplets. The versatility of the method is demonstrated by the synthesis of albumin microspheres, as well as those of the amphiphilic protein casein, the latter being more difficult to prepare by surfactant stabilization techniques. Significant advantages of the method include the avoidance of surfactants which become adsorbed on the particles and influence tissue reactions and drug release, and the ease of removal of the polymeric stabilizer from the final product. The method may find application for the preparation of a wide range of protein and polysaccharide microspheres for medical use.

Animals↗