Browsing by Author "Chandy, T"
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Item Activated charcoal microcapsules and their applications(JOURNAL OF BIOMATERIALS APPLICATIONS, 1998)Activated charcoal, long known to the ancients as a substance of therapeutic value in a variety of maladies, has recently been "rediscovered" to be of great value in medical applications. Activated charcoal hemoperfusion is effective in blood purification for removal of various circulating toxic materials and waste metabolites, directly. However, particulate release and platelet adhesion prevent its continued clinical use. Polymeric coatings or microencapsulation of charcoal within polymers have improved their blood compatibility. Chitosan encapsulated activated charcoal (ACCB) beads have been extensively investigated in our group for the removal of various toxins such as urea, creatinine, uric acid, bilirubin, etc. This article highlights various methods of microencapsulation procedures of activated charcoal and the importance of this novel material for a variety of biomedical applications. Further, this review provides an insight to the future perspectives for using them in clinical practice.Item Changes in pericardial calcification due to antiplatelet agents: In vitro studies(ARTIFICIAL ORGANS, 1998) Chandy, T; Vasudev, SC; Rao, GHRTo develop tissue valves for prolonged use in the cardiovascular system, the complicated process of surface induced calcification must be better understood. Calcification was examined for 60 days on glutaraldehyde treated bovine pericardium (GABP) and enzyme extracted tissues fixed in glutaraldehyde (GATBP) incubated in metastable solutions of calcium phosphate, and the roles of aspirin and persantine in conjunction with vitamins C, B, or E, gentamycin (antibiotic), or pentothal sodium (anesthetic) in the medium were examined. Further, the diffusion of calcium across the GATBP was evaluated using a diffusion cell with 2 compartments. Pericardial calcification was also observed using scanning electron microscopy (SEM) techniques. It seems that the examined antiplatelet agents can modify the pericardial surfaces and subsequently their mineralization processes (GATBP, 31.7 mu g/mg tissue; in the presence of 5 mg% vitamin C, 13.1 mu g/mg tissue; in 1.5 mg% aspirin, 17.2 mu g/mg tissue; and 1 mg% gentamycin, 14.8 mu g/mg tissue) on exposure with the metastable calcium phosphate solution for 60 days. In addition, these agents may modify calcium transport and interfere with the adsorption at the surface, hence reducing calcium nodulation on GATBP. Scanning electron micrographs also revealed a reduction in calcium deposition on the pericardium due to these antiplatelet agents. It may be hypothesized that the influx of calcium on GATBP may be due to the cellular components or the involvement of plasma proteins like the fibrinogen molecule. The exact mechanism of these changes in the calcification of the pericardium are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby for prevention of thrombosis and calcification. However, more in vivo studies are needed to develop applications.Item Changes in polyurethane calcification due to antibiotics(ARTIFICIAL ORGANS, 1996)To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced calcification must be better understood. Calcification was examined on porous polyurethane incubated in metastable solutions of calcium phosphate, and the role of certain antibiotics in the medium was evaluated. It seems that certain aminoglycoside antibiotics can modify polyurethane surfaces and, subsequently, their mineralization process. In addition, these antibiotics may alter the calcium transport through polyurethanes. Therefore, it is conceivable that certain antibiotics can, in addition to producing their antibacterial effect, modulate surface calcium binding by changing the calcium mobilization and crystallization. Additional studies are needed to develop applications.Item Chitosan/calcium alginate microcapsules for intestinal delivery of nitrofurantoin(JOURNAL OF MICROENCAPSULATION, 1996)A new sustained-release dosage form of nitrofurantoin (NF) as microcapsules has been prepared by a mild chitosan/calcium alginate microencapsulation process. These microcapsules have been prepared by adding, dropwise, a solution of sodium alginate containing NF into a chitosan-CaCl2 system. About 70-80% of the drug is released into phosphate buffer, pH = 7.4 within 6 h. Drug release into the gastric medium is found to be relatively slow compared to that into the intestinal medium. From scanning electron microscopic studies, it appears that the chitosan modifies the NF-alginate microspheres. These findings suggest the possibility of modifying the formulation to obtain the controlled release of NF in an oral sustained-delivery system.Item Chitosan/calcium-alginate beads for oral delivery of insulin(JOURNAL OF APPLIED POLYMER SCIENCE, 1996) Hari, PR; Chandy, T; Sharma, CPA mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and insulin, was investigated. The microcapsules were derived by adding dropwise a protein-containing sodium alginate mixture into a chitosan-CaCl2 system. The beads containing a high concentration of entrapped bovine serum albumin (BSA) as more than 70% of the initial concentration were achieved via varying chitosan coat. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within 24 h and no significant release of BSA was observed during treatment with 0.1M HCl pH 1.2 for 4 h. But the acid-treated beads had released almost all the entrapped protein into Tris-HCl pH 7.4 media within 24 h. Instead of BSA, the insulin preload was found to be very low in the chitosan/calcium alginate system; the release characteristics were similar to that of BSA. From scanning electron microscopic studies, it appears that the chitosan modifies the alginate microspheres and subsequently the protein loading. The results indicate the possibility of modifying the formulation in order to obtain the desired controlled release of bioactive peptides (insulin), for a convenient gastrointestinal tract delivery system. (C) 1996 John Wiley & Sons, Inc.Item Controlled release of ferric-magnesium ions from chitosan polyethylene vinyl acetate comatrix for preventing pericardial calcification(DRUG DELIVERY, 1999) Vasudev, SC; Chandy, TFerric and magnesium ions mere embedded in chitosan/polyethylene vinyl acetate comatrix to develop a prolonged release form. The in vitro release profiles of these ions from the comatrix system were monitored in Tris-HCl buffer, pH 7.4, using an ultraviolet (UV) spectrophotometer. The amount of Fe3+ and Mg2+ ions released was initially much higher, followed by a constant slow release profile for a prolonged period, The initial burst release was substantially modified with glutaraldehyde cross-linking of chitosan beads and subsequent styrene butadiene (SBR) coatings on the comatrix. Prostaglandin Fl was immobilized on this matrix via free-radical mechanisms, using Nz plasma to improve their biocompatibility. From scanning electron microscopy studies it appears that the Fe3+/Mg2+ ions diffuse out slowly to the dissolution medium through the micropores of the comatrix. The released Fe3+/Mg2+ ions from the comatrix system had substantially inhibited the pericardial tissue associated calcification, in an in vitro model system. The result proposes the possibility of delivering drug combinations having synergestic effects for therapeutic applications.Item Development of calcification resistant polyurethane via surface modification and drug delivery(PROCEEDING OF THE FIRST REGIONAL CONFERENCE - IEEE ENGINEERING IN MEDICINE & BIOLOGY SOCIETY AND 14TH CONFERENCE OF THE BIOMEDICAL ENGINEERING SOCIETY OF INDIA, 1995) Chandy, T; Sharma, CPItem Development of chitosan/polyethylene vinyl acetate co-matrix: Controlled release of aspirin-heparin for preventing cardiovascular thrombosis(BIOMATERIALS, 1997)Aspirin and heparin were embedded in chitosan/polyethylene vinyl acetate co-matrix to develop a prolonged release form. The in vitro release profiles of these drugs from the co-matrix system were monitored in Tris HCl buffer pH 7.4, using a UV spectrophotometer. The amount of drug release was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with styrenebutadiene coatings. From scanning electron microscopy studies it appears that the drugs diffuse out slowly to the dissolution medium through the micropores of the co-matrix. The released aspirin-heparin from the co-matrix system had shown their antiplatelet and anticoagulant functions. The results propose the possibility of delivering drug combinations, having synergestic effects for therapeutic applications. (C) 1997 Elsevier Science Limited. All rights reserved.Item Effect of alternative crosslinking techniques on the enzymatic degradation of bovine pericardia and their calcification(JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1997)The in vitro calcification and enzymatic degradation of bovine pericardia (BP) after a series of surface treatments were studied as a function of exposure time. The degradation of these treated surfaces was monitored by scanning electron micrography and tensile strength measurements. Polyethylene glycol-(PEG) grafted BP and glutaraldehyde-(GA) treated BPs retained maximum stability in collagenase digestion compared with SDS-treated BP. The ability of cr, chymotrypsin, bromelain, esterase, trypsin, and collagenase to modulate the degradation of SDS-, GA-, PEG-, Carbodiimide-, and glycidylether-treated BPs also was investigated. Incubation of various enzymes to these crosslinked pericardia variably reduced the tensile strength of these tissues. It is conceivable that chemical treatments of pericardial tissues might have altered their physical and chemical configuration and the subsequent degradation properties. In vitro calcification studies showed a substantial reduction in the calcification profile of PEG-grafted bovine pericardia compared to other treated tissues. Furthermore, the biocompatibility aspects of pericardial tissues were established by platelet adhesion and octane contact angle. In conclusion, it seems that the surface modification of bovine pericardia via GA-PEG grafting may provide new ways of controlling biodegradation and calcification. (C) 1997 John Wiley & Sons, Inc.Item Effect of liposome albumin coatings on ferric ion retention and release from chitosan beads(BIOMATERIALS, 1996)Ferric chloride was embedded in a chitosan matrix to develop a prolonged-release form. The in vitro release profiles of ferric ions from chitosan beads were monitored in 0.1 M Tris-HCl buffer, pH 7.4, using a UV spectrophotometer. The amount of drug release was much higher initially, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with liposome and albumin coatings. From scanning electron microscope studies, it appears that the ferric ions diffuse out slowly to the dissolution medium through the micropores of the chitosan matrix. Further, the liposome forms a phospholipid membrane layer in the pores of chitosan beads and encapsulates the ferric ions within their vesicles and controls the release profile. The chitosan beads loaded with ferric ions substantially inhibited the polyurethane-associated calcification, in an in vitro model system. The released ferric ions, appeared to alter the protein-surface binding and improved the biocompatibility of the matrix. The results propose the possibility of modifying the polymer matrix to obtain a desired controlled release of the drug for a prolonged period.Item Effects of double cross-linking technique on the enzymatic degradation and calcification of bovine pericardia(JOURNAL OF BIOMATERIALS APPLICATIONS, 2000)The strength, resorption rates, and biocompatibility of collagenous biomaterials are profoundly influenced by the method of cross-linking. The in vitro and in viuo calcification and enzymatic degradation of bovine pericardia (BP) after a series of surface modifications were studied as a function of exposure time. Collagenase degradations of modified BP were monitored by scanning electron microscopy and tensile strength measurements. Bovine pericardium was modified by a combination of different tissue fixatives such as glutaraldehyde (GA), carbodiimide (EDC), diisocyanate (HMDIC), and polyethylene glycol (PEG). GA-PEG-EDC-PEG and GA-PEG-HMDIC-PEG combination treated BP retained maximum stability in collagenase digestion compared to GATBP. In vitro calcification studies and in vivo rat subcutaneous implantations of modified pericardium have shown substantial reduction in the calcification of double cross-linked BP with PEG modification. Further, the biocompatibility aspects of pericardial tissues were established by platelet adhesion and octane contact angle. It seems that cross-links involving amino and carboxyl residues may provide new ways of controlling biodegradation and calcification.Item Glutaraldehyde treated bovine pericardium: Changes in calcification due to vitamins and platelet inhibitors(ARTIFICIAL ORGANS, 1997)Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B-6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GAFF. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B-6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.Item Influence of polyethylene glycol graftings on the in vitro degradation and calcification of bovine pericardium(JOURNAL OF BIOMATERIALS APPLICATIONS, 1997)Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). This article reports on various chemical techniques for grafting polyethylene glycol (PEG) on bovine pericardium, their biostability, and calcification. The process of calcification profile was studied by in vitro experiments via the incubation of pericardial samples in a metastable solution of calcium phosphate. The calcification profile of PEG-modified bovine pericardium through glutaraldehyde linkages was significantly reduced compared to other methods of grafting. The mechanical property of these PEG-modified tissues after enzyme (collagenase) digestion and calcification were also investigated. PEG grafting of BP via glutaraldehyde or hexamethylene diisocyanate had shown better mechanical stability compared to other grafting methods used.In conclusion, it seems that the surface modification of bovine pericardium through high molecular weight PEGs via glutaraldehyde linkages may provide new ways of controlling tissue biodegradation and calcification.Item Influence of steroid hormones on bovine pericardial calcification(JOURNAL OF BIOMATERIALS APPLICATIONS, 2001)Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GABP). The present investigation describes the influence of steroid hormones in the mineralization of GABP, in an extra-circulatory environment. Calcification was studied on GABP incubation in a metastable solution of calcium phosphate containing steroid hormones such as estrone, progesterone, 7(OH) progesterone, testosterone and beta -estradiol. It is interesting to note that certain steroids can variably increase the GABP calcification. Further, the effect of these steroids in an in vitro hydroxyapatite (HA) formation was investigated. In addition, we observed these steroids alter the calcium transport through GABP in diffusion experiments and also in HA formation. Therefore, it is conceivable that prolonged use of steroids or steroids containing oral contraceptive agents may not be advisable for patients having bioprosthetic implants in contact with blood. A better understanding of the mechanism of these drugs under in vivo conditions is needed to develop applications.Item Inhibition of bioprosthesis calcification due to synergistic effect of Fe/Mg ions to polyethylene glycol grafted bovine pericardium(JOURNAL OF BIOMATERIALS APPLICATIONS, 2001)Calcification has limited the durability of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium (BP). The present study describes calcium antagonistic effect of polyethylene glycol grafted bovine pericardium (PEG-GABP) with Fe2+/Mg2+ delivery from a co-matrix system in rat subcutaneous model. Retrieved samples were biochemically evaluated for calcification and alkaline phosphate (AP) activity. Scanning electron micrographs of 21-day explants had shown excessive calcification with glutaraldehyde treated BP (control). However, the PEG grafting and Fe/Mg release had substantially inhibited the deposition of calcium on BP The extractable alkaline phosphatase activity was also reduced with PEG grafting and metal ion release to BP The extractable AP had shown peak activity at 72 h [for GATBP-250.5 +/-1.2 nm pnp/mg protein/min enzyme activity (unit), PEG-GASP-165.2 +/- 16.6 units], but markedly reduced after 21 days (22.1 +/-1.8 and 12.0 +/-1.5 units, respectively). The initial high levels may be due to tissue injury via surgery, which mitigated with time. It is assumed that ferric ions may slow down or retard the calcification process by the inhibition of proper formation of hydroxy apatite while magnesium ions disrupt the growth of these crystals by replacing Ca2+. In addition it tray be hypothesized that these metal ions may inhibit the key element alkaline phosphatase, which acts as the substrate for mineralization. Hence, it is conceivable that a combination therapy via surface grafting of PEG and local delivery of low levels of ferric and magnesium ions may prevent the bioprosthesis associated calcification.Item Inhibition of platelet adhesion to glow discharge modified surfaces.(Journal of biomaterials applications, 1987)Plasma glow technique has created much interest in the field of surface modification of polymers due to its versatility of generating active polar groups on the surface without affecting the bulk properties. Here an attempt is made to inter-relate the surface properties and platelet adhesion on various polymeric substrates due to plasma treatments. Initially, a critical review of the process and development of thrombosis upon contact of an artificial surface with blood, has been provided, which has been extended with the need for surface modifications to improve their blood compatibility and the versatility of plasma treatments for such modifications have been emphasized. Phospholipids like phosphoryl choline, phosphatidyl choline and phosphoryl ethanolamine were attached to Angioflex surface by plasma glow. The role of such modified substrates to interact with platelets were investigated using Tyrode washed calf platelets. It seems, glow discharge modified phosphoryl choline bilayers dramatically inhibited the platelet-surface binding, which may be due to their biochemical resemblance with thromboresistant surfaces of human blood cells. Further, the behaviour of all phospholipids towards bloodpolymer interaction is not similar and may change depending on the nature of their functional groups, net charge of the phospholipid adsorbed surface and their interaction with platelets and its activation. It is possible to chemically immobilize lipid bilayers on standard polymers, using plasma glow, to improve their biological performance; by suitably selecting the phospholipid combinations.Item Phenyl alanine, tryptophan immobilized chitosan beads as adsorbents for selective removal of immunoproteins.(Journal of biomaterials applications, 1994)The use of adsorbents for the treatment of patients suffering from various immune diseases is still in its infancy. Therefore, the development of selective absorbents for the removal or decrease of immunoproteins from plasma is of great importance. In this study, chitosan, a natural polysaccharide having structural characteristics similar to glycosamino glycans, which is non-toxic and biocompatible, has been used for protein adsorption studies. Amino acids like phenyl alanine and tryptophan in different ratios are bonded to these polymers to observe immunoadsorption. Several layers of phenyl alanine or tryptophan have been coated covalently on chitosan beads using N2-plasma, carbodiimide or glutaraldehyde treatments. Scanning electron micrographs have revealed the surface morphological changes after such modifications. The surface modified chitosan beads have exhibited high binding affinity for gamma-globulin compared to bare beads. It is also observed that the amount of fibrinogen adsorption is reduced on modified substrate. A selective removal of IgG and IgM has also been observed with these modified matrix when tested with human plasma, using immuno diffusion methods. The modified chitosan membranes have demonstrated a reduction in platelet attachment, showing that these substrates have become more blood compatible. Hence, it appears that modified chitosan surfaces may be an excellent sorbent system for haemoperfusion due to their high binding affinity for immunoproteins and blood compatibility. Further studies are needed to determine the behaviour under clinical conditions.Item Polyethylene glycol-grafted bovine pericardium: a novel hybrid tissue resistant to calcification(JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 1999)Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). An investigation was made of the grafting of different molecular weight polyethylene glycol (PEG 600, 1500, 4000 and 6000) via glutaraldehyde (GA) linkages to bovine pericardium (BP) and of their stability and calcification. The process of the calcification profile was studied by in vitro experiments via incubating pericardial samples in a metastable solution of calcium phosphate. Calcification of bovine pericardium grafted with PEG 6000 was significantly decreased compared to low molecular weight PEG grafts or Sodium dodecyl sulphate- (SDS) and GA-treated tissues. The mechanical properties of these modified tissues after enzyme (Trypsin) digestion and calcification were investigated. The biocompatibility aspects of grafted tissues were also established by monitoring the platelet adhesion, octane contact angle and water of hydration. PEG 6000-grafted tissues retained the maximum strength in trypsin buffer and calcium phosphate solutions. Scanning electron micrographs revealed that the PEG-grafted bovine pericardium had substantially inhibited the platelet-surface attachment and their spreading. It is conceivable that high molecular weight polyethylene glycol-grafted pericardium (a hybrid tissue) may be a suitable calcium-resistant material for developing prosthetic valves due to their stability and biocompatibility. (C) 1999 Kluwer Academic Publishers.Item Structural studies on bovine bioprosthetic tissues and their in vivo calcification: Prevention via drug delivery(BIOMATERIALS, 1996)Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end-stage phenomenon affecting a wide variety of bioprostheses. To study the process of calcification in tissue prosthetics, glutaraldehyde-treated bovine pericardium, dura mater and fascialata were implanted subcutaneously in rats and retrieved 21 days later and thereby morphological findings were correlated with biochemically determined levels of calcium. Transmission electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The deposition of calcium was higher with dura and fascia prostheses compared to pericardium. However, the release of Fe3+ ions from chitosan matrix had substantially inhibited the deposits of calcium in all implanted tissues. It seems that the structural and anatomical features of the tissue is one of the important factors for tissue-associated calcification. It is also confirmed that glutaraldehyde-preserved pericardium is the most suitable material for the development of cardiac prosthesis, with an appropriate drug combination therapy for prevention of pathological calcification.Item Synergistic effect of released aspirin/heparin for preventing bovine pericardial calcification(ARTIFICIAL ORGANS, 2000)Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). Aspirin, a potent antiplatelet drug, and heparin, an anticoagulant, are commonly used for postimplant complications such as thrombosis and thromboembolism. Aspirin and heparin were embedded in chitosan/polyethylene vinylacetate co-matrix to develop a prolonged release form. The effect of these drugs towards the bioprosthetic calcification was investigated by in vitro and in vivo models. In vitro and in vivo evaluation suggest that the released aspirin/heparin from the co-matrix had a synergistic effect in inhibiting GATBP calcification. In vivo subcutaneous coimplantation was performed with PEG-20,000 grafted bovine pericardium (PEG-GABP), aspirin, and heparin. Biochemical, histological, and scanning electron microscopic evaluation of retrieved samples demonstrated a significant reduction in calcium deposition and alkaline phosphatase activity on PEG-GABP compared to GATBP. It seems that the aspirin/heparin combination synergistically inhibits the pericardial calcification in addition to their antithrombotic function.