Browsing by Author "CHANDY, T"

Now showing 1 - 20 of 26
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    ANESTHETIC AND FERRIC-MAGNESIUM ION COMBINATIONS AS CALCIUM-ANTAGONISTS FOR GLUTARALDEHYDE-TREATED PERICARDIAL TISSUES
    (CLINICAL MATERIALS, 1994)
    The principal cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated bovine pericardial valves is calcification. The present investigation describes the mineralization of glutaraldehyde-treated bovine pericardium (GBP), in an extra-circulatory environment and the possible methods of prevention via metal ions. Calcification was examined on GBP incubated in metastable solutions of calcium phosphate and the role of certain anesthetic drugs, ferric ions and magnesium ions in the media was evaluated. It seems that the addition of ethyl alcohol, pentothal and xylocaine in the calcium phosphate solutions, variably inhibited the GBP calcification. The metals like Fe3+ ions and Mg2+ ions and their combinations also substantially reduced the GBP mineralization. It is assumed that ferric ions may slow down or retard the calcification process by delaying the proper formation of hydroxyapatite while magnesium ions disrupt the growth of these crystals by replacing Ca2+. Hence, it is conceivable that a combination therapy-via local delivery of low levels of ferric ions and magnesium ions-may prevent the GBP-associated calcification.Further, a very low daily intake of alcohol appears to be beneficial to reduce the profile of calcium deposition at tissue interfaces.
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    BIODEGRADABLE CHITOSAN MATRIX FOR THE CONTROLLED RELEASE OF STEROIDS
    (BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY, 1991)
    Chitosan, a polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to be nontoxic and bioabsorbable. This study highlights the use of chitosan matrix for controlled drug delivery systems. The steroid drugs, namely testosterone, progesterone and beta-oestradiol were mixed with chitosan and the films were prepared by evaporation technique. The in vitro release profile of these steroids from the film matrix was monitored, as a function of time, in phosphate buffered saline (PBS, pH 7.4) at 37 degree C using a U-V-spectrophotometer. The degradation, of these chitosan and drug loaded chitosan films, was also investigated by weight loss and tensile strength studies. The steroid release from chitosan films was compared with the release of these drugs from their microbeads. It appears, the films and the microbeads stayed intact during the dissolution study of 90 days and the possibility of using these systems in contraceptive applications and novel drug delivery systems are discussed.
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    CHITOSAN - AS A BIOMATERIAL
    (BIOMATERIALS ARTIFICIAL CELLS AND ARTIFICIAL ORGANS, 1990)
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    CHITOSAN BEADS AND GRANULES FOR ORAL SUSTAINED DELIVERY OF NIFEDIPINE - INVITRO STUDIES
    (BIOMATERIALS, 1992)
    Nifedipine was embedded in a chitosan matrix to develop a prolonged-release form. The in vitro release profiles of nifedipine from chitosan beads and microgranules were monitored by UV spectrophotometer. The studies were performed in a rotating shaker (100 rev min-1) in 0.1 M HCl buffer (pH 2.0) or 0.1 M phosphate buffer (pH 7.4). Comparison was made between drug-loaded microbeads and microgranules. The amount and percentage of drug release were much higher in HCI than in phosphate buffer, probably due to the salt formation of the matrix (chitosan hydrochloride) at acid pH. The release rate of nifedipine from chitosan matrix was slower for beads than granules. These findings suggest the possibility of modifying the formulations to obtain the desired controlled release of the drug in an oral sustained-delivery system.
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    CHITOSAN MATRIX FOR ORAL SUSTAINED DELIVERY OF AMPICILLIN
    (BIOMATERIALS, 1993)
    Ampicillin was embedded in a chitosan matrix to develop an oral release dosage form. The in vitro release profile of ampicillin from chitosan beads and microgranules of chitosan was monitored, as a function of time, using a UV Spectrophotometer. The releasing studies were performed in a rotating shaker at 100 r.p.m., containing 0.1 M HCl buffer, pH 2.0, or 0.1 M phosphate buffer, pH 7.4, solutions, and a comparison was made between the drug loaded microbeads and microgranules. It seems that the amount and percentage of drug release was much higher in HCl solution compared with the phosphate solution, probably due to the gelation properties of the matrix at acid pH. The release rate of ampicillin from the chitosan matrix was slower for the beads as compared with the granules. From scanning electron microscopic studies, it appears that the drug forms a crystal structure within the chitosan beads, which dissolves out slowly to the dissolution medium through the micropores of the chitosan matrix. The results propose the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system.
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    EFFECT OF PLASMA GLOW, GLUTARALDEHYDE AND CARBODIIMIDE TREATMENTS ON THE ENZYMATIC DEGRADATION OF POLY(L-LACTIC ACID) AND POLY(GAMMA-BENZYL-L-GLUTAMATE) FILMS
    (BIOMATERIALS, 1991)
    The hydrolytic and enzymic degradation of poly(L-lactic acid) (PLA) and poly(gamma-benzyl L-glutamate) (PBGA) films, together with a series of surface treatments, were studied, as a function of exposure time. The degradation of these polymers was monitored by weight loss, contact angle, pH changes and tensile strength studies. Glutaraldehyde treatment retained the maximum strength of PLA in buffer, followed by carbodiimide, compared with control films. On the other hand, plasma glow reversed the effect. The ability of alpha-chymotrypsin, carboxypeptidase, ficin, esterase, bromelain and leucine aminopeptidase to modulate the degradation of PLA and PBGA was also investigated. Addition of these enzymes to the polymer-buffer system reduced the tensile strength of these polymers variably. Among the six enzymes studied, leucine aminopeptidase showed the highest enzymic effect on the degradation of the glutaraldehyde-treated and bare PLA or bare PBGA films. However, glutaraldehyde-cross-linked PLA demonstrated maximum stability in buffers or in all other enzyme systems studied compared with bare PLA. It is conceivable that surface treatments on these polymers might have altered their physical and chemical configuration and the subsequent degradation properties. Surface modifications may provide new ways of controlling the biodegradation of polymers for a variety of biomedical applications.
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    EFFECTS OF LIPOPROTEINS ON PROTEIN PLATELET INTERACTION ON POLYMERS
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1991)
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    ERYTHROCYTES IMMOBILIZED PROTEINATED SUBSTRATES - STABILITY DUE TO GLOW-DISCHARGE
    (ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1990) CHANDY, T; SHARMA, CP
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    GLUCOSE-RESPONSIVE INSULIN RELEASE FROM POLY(VINYL ALCOHOL)-BLENDED POLYACRYLAMIDE MEMBRANES CONTAINING GLUCOSE-OXIDASE
    (JOURNAL OF APPLIED POLYMER SCIENCE, 1992) CHANDY, T; SHARMA, CP
    Glucose-sensitive membranes that can increase their permeability in the presence of glucose have been developed. Membranes are fabricated by free-radical polymerization of acrylamide and poly (vinyl alcohol) blends, containing glucose oxidase (GOD). The polymers are hydrogels, with water content in the range of 85-95%, depending on the pH or glucose concentration. The gluconic acid produced by an enzymatic reaction between glucose oxidase and glucose induces a decrease in pH value of the medium. This may causes the protonation of the amino groups in the membrane, resulting in an increase in water content of the polyamine membrane or which changes the solubility of insulin and the diffusional driving force. The in vitro retention of the enzyme activity by the membrane is also reported. It appears that the problem of membrane rupture may be alleviated by the blending of polyacrylamide (AA) with poly(vinyl alcohol) (PVA), since they have demonstrated an improved wet strength, without altering their insulin-transport properties. This preliminary report proposes the possibility of developing glucose-sensitive membranes for controlled delivery of insulin and also benefits from ongoing research on biosensors.
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    HEPARIN IMMOBILIZED CHITOSAN-POLYETHYLENEGLYCOL INTERPENETRATING NETWORK - ANTITHROMBOGENICITY
    (ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 1995)
    This work deals with the synthesis and blood compatibility studies of Heparin immobilized chitosan polyethyleneglycol (Chit-PEG) hydrogels for various biomedical applications. Chit-PEG interpenetrating net work (IPN) had been synthesised by crosslinking different ratios of chitosan with glutaraldehyde using schiffs base reaction mechanism and interpenetrating polyethyleneglycol (PEG) to form hydrogen bonding between the amino hydrogen in chitosan and polyether oxygen.An optimum gel combination was selected from the IPN of Chit-PEG and used for bonding heparin. This modified gel had dramatically improved its blood compatibility. The antithrombotic function of this gel and the release profile of heparin had been investigated using coagulation assays, and spectrophotometric quantitation. Recalcification times of plasma exposed to heparin immobilized Chit-PEG hydrogel were markedly increased as compared to heparin free gels. The anticoagulant function of this gel matrix may be due to partially released heparin and bonded heparin.
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    INFLUENCE OF ANTIHYPERTENSIVE DRUGS AND STEROID-HORMONES ON PROTEIN ADSORPTION DESORPTION ON POLYCARBONATE
    (ARTIFICIAL ORGANS, 1991)
    To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced thrombosis needs to be better understood. It is documented that certain antihypertensive drugs can inhibit platelet adhesion to an artificial surface; on the other hand, steroid drugs increase platelet surface attachment to variable degrees. This study demonstrates the changes in protein-surface binding with certain antihypertensive and antianginal drugs-namely, digoxin, sorbitrate, thyroxine, sembrina and hydralazine-and five steroid hormones-estrone, progesterone, beta-estradiol, 7(OH) progesterone, and testosterone-using trace labelling methods. It seems that the addition of these antihypertensive drugs to the polymer-protein system has increased the level of surface-bound albumin and reduced the fibrinogen surface concentration to variable degrees. A reversed pattern of protein-surface attachment has been evident with steroid hormones. Thus, it appears that the changes in platelet attachment due to various drugs may be dependent on the availability of fibrinogen receptors at the polymer interface, along with other possible biological factors. Prolonged use of antihypertensive drugs may not have any significant side effect for patients having an implant. However, the use of steroids or steroid-containing oral contraceptive agents may not be advisable for patients having an artificial implant in contact with blood. A better understanding of the mechanism of these drugs under in vivo conditions is needed to correlate these findings.
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    INHIBITION OF IN-VITRO CALCIUM-PHOSPHATE PRECIPITATION IN PRESENCE OF POLYURETHANE VIA SURFACE MODIFICATION AND DRUG-DELIVERY
    (JOURNAL OF APPLIED BIOMATERIALS, 1994)
    Biomaterial associated calcification is the principal cause of the clinical failure of bioprosthetic implants. The present investigation describes the mineralization of polymeric substrate in an extracirculatory environment and the possible methods of prevention. Calcification was examined on various polyurethane films (and bioprosthetic tissue) incubated in metastable solutions of calcium phosphate and the role of polymer casting and precipitation was evaluated. The formulation and the in vitro efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents, such as Fe+++ or protamine sulfate (PS), were also attempted. The in vitro release profiles of PS from chitosan beads was performed in a rotating shaker (100 rpm) in 0.1 M phosphate buffer (pH 7.4) and was monitored spectrophotometrically. The amount and percentage of drug release were much higher initially, which was controlled with the incorporation of egg phosphatidyl choline (EPC). The PS loaded chitosan beads (coincubated in calcium phosphate solution with the calcifiable polyurethane films) significantly inhibited biomaterial calcification (about 40-50% inhibition). Surface modification of polyurethanes with Fe+++ or PS also inhibited the calcification profile of the material. These findings suggest the possibility of a combination therapy for prevention of biomaterial associated calcification via surface modifications in conjunction with long-term controlled release of the anticalcifying drugs. (C) 1994 John Wiley & Sons, Inc.
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    LIPOPROTEIN ADSORPTION ONTO MODIFIED CHITOSAN BEADS - PRELIMINARY-STUDY
    (BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY, 1993)
    Amoung the currently used LDL - apheresis techniques selective removal seems to be a better option. We have made a preliminary study on adsorption of LDL onto modified and bare chitosan and PVA beads. It seems that bare chitosan itself maybe an exellent adsorbent system for LDL. Further detailed studies are required to examine the specificity and selectivity in adsorption.
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    POLYELECTROLYTE MEMBRANES FROM CHITOSAN
    (ACTA POLYMERICA, 1990) MAI, PT; CHANDY, T; SHARMA, CP; PAUL, D; SCHWARZ, HH
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    POLYLYSINE-IMMOBILIZED CHITOSAN BEADS AS ADSORBENTS FOR BILIRUBIN
    (ARTIFICIAL ORGANS, 1992)
    Hyperbilirubinemia generally relates to an elevated bilirubin level in the blood and is usually an indication of a disease of the blood, liver, or biliary tract. Hemoperfusion using synthetic resins as sorbents has been one of the ways to reduce bilirubin. In this study, chitosan, a natural polysaccharide having structural characteristics similar to glycosaminoglycans and which is nontoxic and biocompatible, has been used for bilirubin binding. Several layers Of poly-L-lysine have been coated covalently onto chitosan beads, using N2 plasma and carbodiimide treatments. Such surface-modified chitosan beads exhibited high binding affinities for bilirubin (1.13 +/- 0.18 mg/g beads) in aqueous phosphate buffer solutions at 4-degrees-C in relation to activated charcoal (0.74 +/- 0.2 mg/g). The polylysine-coated resins have been reported to have an improved binding affinity for bilirubin over cholestyramine. It seems that the surface-immobilized polylysine has an increased bilirubin binding affinity and is highly stable. The binding capacity is proportional to the amount of polylysine bonded to the chitosan beads. The hemolytic potential of all modified beads is compatible with polystyrene control tubes. Studies were also performed against albumin as proof of specificity toward bilirubin binding. The albumin-coated beads have shown the highest blood compatibility and selectivity over the other modified beads. However, it appears that polylysine-modified chitosan may be an excellent sorbent system for hemoperfusion due to its high binding affinity, capacity, and blood compatibility. Further studies are needed to determine its behavior under clinical conditions.
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    PREPARATION AND PERFORMANCE OF CHITOSAN ENCAPSULATED ACTIVATED-CHARCOAL (ACCB) ADSORBENTS FOR SMALL MOLECULES
    (JOURNAL OF MICROENCAPSULATION, 1993)
    A technique is described to encapsulate activated charcoal for haemoperfusion to be used in an artificial liver support. Activated charcoal was encapsulated within chitosan matrix (ACCB) in different concentrations, and was used as the supports for perfusion of a mixture of solutes, having molecular weight ranges from 60 to 69000; under a flow rate of 8 ml/min. It seems the ACCB may be a good adsorbent system for the removal of toxic uric acid, creatinine, bilirubin, etc., from solutions; while larger molecules such as albumin are adsorbed less. The encapsulated charcoal did not leach out from the matrix during perfusion, and the system may be useful for detoxification of blood. The haemolytic potential of ACCB has been compatible with polystyrene control tubes. However, further studies are needed to determine their behaviour under clinical conditions.