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Biomedical subjects

T Chandy

Publications and source records attributed to T Chandy.

At least 37 records · Page 2Linked to original sources

Influence of polyethylene glycol graftings on the in vitro degradation and calcification of bovine pericardium.

Calcification is a frequent cause of the clinical failure of bio-prosthetic 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.

Animals↗

Effect of liposome-albumin coatings on ferric ion retention and release from chitosan beads.

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.

Albumins↗

Structural studies on bovine bioprosthetic tissues and their in vivo calcification: prevention via drug delivery.

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.

Animals↗

Changes in polyurethane calcification due to antibiotics.

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.

Aminoglycosides↗

Heparin immobilized chitosan--poly ethylene glycol interpenetrating network: antithrombogenicity.

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.

Animals↗

Inhibition of in vitro calcium phosphate precipitation in presence of polyurethane via surface modification and drug delivery.

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.

Calcification, Physiologic↗

Anesthetic and ferric-magnesium ion combinations as calcium antagonists for glutaraldehyde-treated pericardial tissues.

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.

Anesthetics↗

Phenyl alanine, tryptophan immobilized chitosan beads as adsorbents for selective removal of immunoproteins.

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.

Adsorption↗

Chitosan matrix for oral sustained delivery of ampicillin.

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 HCI 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 HCI 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.

Administration, Oral↗

Lipoprotein adsorption onto modified chitosan beads: preliminary study.

Among 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 excellent adsorbent system for LDL. Further detailed studies are required to examine the specificity and selectivity in adsorption.

Animals↗

Chitosan beads and granules for oral sustained delivery of nifedipine: in vitro studies.

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 HCl 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.

Administration, Oral↗

Polylysine-immobilized chitosan beads as adsorbents for bilirubin.

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.

Adsorption↗

Effect of plasma glow, glutaraldehyde and carbodiimide treatments on the enzymic degradation of poly (L-lactic acid) and poly (gamma-benzyl-L-glutamate) films.

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.

Biocompatible Materials↗

Biodegradable chitosan matrix for the controlled release of steroids.

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.

Biocompatible Materials↗

Influence of antihypertensive drugs and steroid hormones on protein adsorption/desorption on polycarbonate.

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.

Antihypertensive Agents↗

Chitosan--as a biomaterial.

Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.

Animals↗

The influence of vaccines and hyper immune serums on protein/platelet interaction towards an artificial surface.

Protein adsorption and platelet adhesion are two important biological processes arising at the blood prosthetic interface. The effect of certain commonly used vaccines and hyper immune serums namely tetanus toxoid, tetanus immunoglobulin, polyvalent anti-snake venum serum and anticholera vaccine to modulate the surface induced platelet adhesion to polycarbonate substrate was investigated using washed calf platelets in presence and absence of fibrinogen. This study also demonstrated the changes in protein-surface binding with few of these vaccines, using SDS - polyacrylamide gel electrophoresis. It seems, the addition of tetanus toxoid to the polymer-protein system increased the level of surface-bound albumin and reduced the fibrinogen-surface attachment. On the other hand, tetanus immunoglobulin reversed the effect. This itself may be one of the parameters for the observed reduction in platelet-surface attachment due to tetanus toxoid. The enhanced platelet adhesion with other vaccines, may be correlated with the availability of more fibrinogen receptors for the platelets to attach. A better understanding of the mechanism of these vaccines is needed in vivo conditions for interrelating these findings.

Adsorption↗