Immobile plasticizer in flexible PVC.
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Alkanes↗
Biomedical subjects
A Jayakrishnan
Publications and source records attributed to A Jayakrishnan.
Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system.
Smooth, highly spherical, crosslinked chitosan microspheres in the size range of 45-300 microns loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersion of chitosan containing progesterone in a non-aqueous dispersion medium consisting of liquid paraffin and petroleum ether stabilized using sorbitan sesquioleate. In vitro release of the drug into phosphate buffer at 37 degrees C was determined as a function of crosslinking density of the microspheres and particle size. The extent of drug release had a remarkable dependence on the crosslinking density of the microspheres, the highly crosslinked spheres releasing only around 35% of the incorporated steroid in 40 days compared to 70% from spheres lightly crosslinked. Determination of the in vivo bioavailability of the steroid from microsphere formulation by intramuscular injection in rabbits showed that a plasma concentration of 1 to 2 ng/ml was maintained up to 5 months without a high 'burst effect'. Data obtained suggest that the crosslinked chitosan microspheres would be an interesting system for long term delivery of steroids.
Animals↗
Migration resistant, blood-compatible plasticized polyvinyl chloride for medical and related applications.
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 hepatocarcinogens, 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 polyethylene 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 plasticizer migration from PVC cling films and polyvinylidene chloride films used extensively in food packaging.
Animals↗
Protein release from poly(epsilon-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: a comparative study.
Poly(epsilon-caprolactone) (PCL) microspheres containing c. 3% bovine serum albumin (BSA) were prepared by melt encapsulation and solvent evaporation techniques. PCL, because of its low Tm, enabled the melt encapsulation of BSA at 75 degrees C thereby avoiding potentially toxic organic solvents such as dichloromethane (DCM). Unlike the solvent evaporation method, melt encapsulation led to 100% incorporation efficiency which is a key factor in the microencapsulation of water-soluble drugs. Examination of the stability of the encapsulated protein by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that protein integrity was unaffected by both methods of encapsulation. In vitro release of the protein into phosphate buffer examined at 37 degrees C from microspheres prepared by both techniques showed that the release rate from melt-encapsulated microspheres was somewhat slower compared to the release from solvent-evaporated spheres. Both released around 20% of the incorporated protein in 2 weeks amounting to approximately 6.5 micrograms mg-1 of microspheres. Although the diffusivity of macromolecules in PCL is rather low, it is shown that PCL microspheres are capable of delivering sufficient quantity of proteins by diffusion for prolonged periods to function as a carrier for many vaccines. Unlike poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) polymers which generate extreme acid environments during their degradation, the delayed degradation characteristics of PCL do not generate an acid environment during protein release and, therefore, may be advantageous for sustained delivery of proteins and polypeptides.
Animals↗
Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices.
The use of glutaraldehyde as a fixative in bioprostheses and drug delivery matrices is reviewed. The chemistry of glutaraldehyde cross-linking and its effect on the biological performance of a number of bioprostheses such as tissue heart valves, vascular grafts, pericardial patches, tendon grafts and drug delivery matrices are examined.
Biomechanical Phenomena↗
Antitumour activity of mitoxantrone-loaded chitosan microspheres against Ehrlich ascites carcinoma.
Glutaraldehyde cross-linked chitosan microspheres containing the antineoplastic agent mitoxantrone were prepared and the antitumour activity was evaluated against Ehrlich ascites carcinoma in mice by intraperitoneal injections. The tumour inhibitory effect was followed by monitoring animal survival time and change in body weight for a period of 60 days. While the mean survival time of animals which received 2 mg and 1 mg of free mitoxantrone intraperitoneally was 2.1 and 4.6 days, respectively, animals which received 2 mg mitoxantrone via microspheres showed a mean survival time of 50 days. Five out of 8 animals treated using microspheres lived beyond 60 days. The percentage ratio mean survival time of the treated group divided by the mean survival time of the untreated group for animals treated using mitoxantrone-loaded chitosan microspheres containing 2 mg of the drug was 290 compared with 12.2 for those which received 2 mg of the free drug. The antitumour effect of mitoxantrone-loaded microspheres against Ehrlich ascites carcinoma was much higher than that of doxorubicin-loaded microspheres reported by previous workers. Our data demonstrate the potential of mitoxantrone-loaded chitosan microspheres for sustained drug delivery to minimize drug toxicity and maximize therapeutic efficacy.
Animals↗
Glutaraldehyde cross-linked chitosan microspheres as a long acting biodegradable drug delivery vehicle: studies on the in vitro release of mitoxantrone and in vivo degradation of microspheres in rat muscle.
Chitosan microspheres were prepared from 74% deacetylated chitin by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in a mixture of liquid paraffin and petroleum ether stabilized using sorbitan sesquioleate as the surfactant. Cross-linking and hardening of the spherical particles were achieved by the addition of glutaraldehyde-saturated toluene through the organic phase. A relatively novel antineoplastic agent, mitoxantrone, was incorporated into the microspheres and the drug release was studied in vitro into phosphate buffer for over 4 weeks at 27 degrees C. Drug release was found to be effectively controlled by the extent of cross-linking. Only about 25% of the incorporated drug was released over 36 days from microspheres of high cross-linking density. Implantation of placebo chitosan microspheres in the skeletal muscle of rats was carried out in order to assess the biocompatibility and biodegradability of the microspheres. Histological analysis showed that the microspheres were well tolerated by the living tissue. However, no significant biodegradation of the material was noticed over a period of 3 months in the skeletal muscle of rats. Data obtained indicate the possibility of using cross-linked chitosan microspheres as a drug carrier for sustained drug release for very long periods.
Animals↗
Glutaraldehyde cross-linked bovine casein microspheres as a matrix for the controlled release of theophylline: in-vitro studies.
A controlled release dosage form of theophylline in the form of microspheres using the milk protein casein as the matrix is described. Glutaraldehyde cross-linking of an aqueous alkaline solution of the protein containing the drug, dispersed in a mixture of dichloromethane/hexane having ca. 1% of an aliphatic polyurethane as the suspension stabilizer, led to the formation of the drug-loaded microspheres. Drug incorporation efficiency of around 80% could be achieved by the technique. Release profiles of the drug were examined in simulated gastric and intestinal fluids at 37 degrees C. It was observed that the release was diffusion-controlled and followed the Higuchi model. Release characteristics were influenced by the cross-linking density, particle size and the extent of loading. Data obtained indicate that the natural milk protein casein could be used as a matrix for sustained release oral dosage forms.
Animals↗
Casein as a carrier matrix for 5-fluorouracil: drug release from microspheres, drug-protein conjugates and in-vivo degradation of microspheres in rat muscle.
Glutaraldehyde cross-linked casein microspheres were loaded with 5-fluorouracil (5-FU) from concentrated aqueous solutions of the drug after the microspheres were synthesized and cleaned. In-vitro release of the drug was examined in phosphate buffer in the absence and in the presence of protease at 37 degrees C. Drug release data showed that only about 20% of the drug is released in the absence of protease even after 5 days, while digestion of the matrix with protease released the entrapped drug completely in about 24 h. A protein-drug conjugate was synthesized via carbamoyl linkage using 6-(5-FU-1-yl)hexyl isocyanate and the drug release was examined in phosphate buffer at 37 degrees C. Release from the protein-5-FU conjugate was slower compared with the release from microspheres in the presence of protease. Implantation of placebo microspheres of different cross-linking densities in the gluteal muscle of rats showed no adverse tissue reactions over a one-year period. Histopathological examination of the tissues containing injected microspheres suggested that the biological life of casein microspheres in muscle is about 6 months, which is three times that of cross-linked albumin microspheres.
Albumins↗
Cross-linked chitosan microspheres as carriers for prolonged delivery of macromolecular drugs.
Bovine serum albumin (BSA) and diphtheria toxoid (DT) were loaded by passive absorption from aqueous solutions into preformed glutaraldehyde cross-linked chitosan microspheres. In vitro release of BSA under sink conditions at 37 degrees C showed that even though there was a large burst effect, there was a more or less steady increase with time thereafter for several days. Coating the BSA-loaded particles with paraffin oil or with a polymer, such as polylactic acid, modulated drug release. After the initial burst from PLA coated particles, the release rate increased with time for nearly 2 months. Preliminary immunogenicity studies on Wistar rats using DT loaded chitosan spheres showed that the antibody titres were fairly constant over a 5-month period, although very low compared to DT given on alum as control. Histological studies of placebo microspheres intramuscularly injected into rats demonstrated their tissue compatibility. Biodegradation was not complete in 6 months demonstrating the potential of cross-linked chitosan spheres as a long-acting drug delivery vehicle. The study demonstrated the possibility of incorporating biological macromolecules which are very sensitive to organic solvents, pH, temperature, ultrasound, etc. by a passive absorption technique to degradable biopolymer matrices thereby preserving their biological integrity. It is also shown that drugs passively absorbed into such matrices by taking advantage of their swelling behaviour need not necessarily be released completely in the initial 'burst' and a sustained release may be possible for macromolecules thus incorporated.
Animals↗
Controlled release of oral drugs from cross-linked polyvinyl alcohol microspheres.
A new technique for the preparation of cross-linked polyvinyl alcohol (PVA) microspheres containing various drugs is described. An aqueous solution of PVA containing various concentrations of glutaraldehyde was dispersed as droplets in liquid paraffin using a suitable stabilizing agent. Cross-linking of PVA droplets with glutaraldehyde was induced by an acid catalyst (HCl) which was produced by the addition of small quantities of benzoyl chloride into the dispersion medium. Microspheres containing drugs such as aspirin, griseofulvin and nicotinic acid were prepared by carrying out the cross-linking reaction in the presence of such drugs. The drug release studies were carried out in simulated gastric and intestinal fluids without enzymes at 37 degrees C. It was observed that increase in the cross-linking density of the microspheres reduced the drug release rate considerably, suggesting that the release profiles could be controlled by changing the cross-linking density. It was also observed that a higher rate of release was obtained from smaller beads.
Aspirin↗
Oral sustained-release drug delivery systems using polycarbonate microspheres capable of floating on the gastric fluid.
Polycarbonate microspheres loaded with aspirin, griseofulvin and p-nitroaniline were prepared by a solvent evaporation technique. High drug loading (> 50%) was achieved by this process. Drug-loaded microspheres were found to float on simulated gastric fluid and intestinal fluid. Drug-release studies were carried out in these fluids at 37 degrees C. Increasing the drug to polymer ratio in the microspheres increased both their mean particle size and the release rate of the drugs. It was concluded that sustained delivery of drugs could be effected using this matrix.
Aniline Compounds↗
Synthesis, properties, and intratumoral evaluation of mitoxantrone-loaded casein microspheres in Lewis lung carcinoma.
Smooth, round, uniform bovine casein microspheres of 1-5 and 10-20 microns size were readily prepared by a steric stabilization technique previously developed in this laboratory for synthesis of albumin microspheres. The avid phagocytic uptake of casein and albumin microspheres was demonstrated with fluorescein-labelled microspheres using a macrophage-like mouse myelomonocytic leukaemia cell line. Post-synthesis loading of 25% mitoxantrone was achieved for casein microspheres containing 20% polyglutamic acid. Preliminary intratumoural chemotherapy experiments with a mouse Lewis lung carcinoma indicated that mitoxantrone and mitoxantrone-loaded casein-polyglutamic acid microspheres exhibited lower toxicity when administered intratumorally.
Animals↗
Histopathological evaluation of polymethyl methacrylate as an embolic agent.
Polymethyl methacrylate (PMMA) microspheres were used as an embolic agent to reduce the vascularity in eight patients with intracranial vascular tumours. Post embolization angiograms showed 30-60% reduction in the vascularity of the tumours. No patient developed any neurological complications in the immediate post-embolization period. These eight patients subsequently underwent surgery for the removal of their tumours. During surgery there was minimal blood loss and a good plane of cleavage was obtained between the tumour and the adjacent brain. The surgical specimens were examined histopathologically for the effects of PMMA. PMMA microspheres, in contrast to other cyanoacrylates--isobutyl-2-cyanoacrylate (IBCA)--did not elicit either inflammatory reaction or mural angionecrosis within the wall of the embolised vessels. The histopathological studies suggest that PMMA microspheres are an inert material and can be used as an adjunct in the management of intracranial vascular tumours.
Adult↗
Cross-linked chitosan microspheres: preparation and evaluation as a matrix for the controlled release of pharmaceuticals.
Chitosan 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 degrees 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.
Aspirin↗
Radiation grafting of hydrophilic monomers on to plasticized poly(vinyl chloride) sheets. II. Migration behaviour of the plasticizer from N-vinyl pyrrolidone grafted sheets.
The grafting of N-vinyl pyrrolidone, a hydrophilic monomer, on to flexible poly(vinyl chloride) sheets used in medical applications using ionizing radiation from a 60Co source was studied. The graft yield was found to increase linearly with monomer concentration and also with increasing radiation doses. The migration of the plasticizer di-(2-ethylhexyl)phthalate into a strong organic extractant such as n-hexane was studied at different time intervals for different grafted systems of poly(vinyl chloride) at 30 degrees C. The results indicated a drastic reduction in the leaching of the plasticizer from grafted systems versus ungrafted controls. Incorporation of ethylene dimethacrylate cross-linker during grafting did not seem to affect the graft yield considerably but appeared to further reduce the plasticizer migration. Surface energy calculations of the grafted samples indicate that the surfaces are highly hydrophilic compared to ungrafted poly(vinyl chloride) and the polar and dispersion components tend to vary with increasing cross-linker concentration.
Biocompatible Materials↗
Tantalum-loaded polyurethane microspheres for particulate embolization: preparation and properties.
Polyurethane microspheres having diameters in the range 150-1500 microns were prepared by condensation polymerization of toluene diisocyanate (TDI) with poly(tetramethylene glycol) (PTMG) of average mol wt 990 in an aqueous dispersion medium containing dioctyl sulphosuccinate (DOS) as the suspension stabilizer and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the catalyst for polymerization. Incorporation of tantalum powder in the polymerizing phase led to the formation of Ta-loaded microspheres with good radiopacity. Microspheres were surface-modified by grafting methacrylic acid (MA) on to them using gamma-radiation from a Co60 source. Conversion of the grafted MA into its sodium salt imparted hydrophilicity and slipperiness to the microspheres enabling them to pass through Teflon catheters without obstructing the catheter lumen. These microspheres may find application as radiopaque embolization agents.
Biocompatible Materials↗
Hydrolysed microspheres from cross-linked polymethyl methacrylate (Hydrogel). A new embolic material for interventional neuroradiology.
Highly hydrophilic, perfectly smooth and spherical microspheres have been synthetized. These non-biodegradable microspheres absorb water in varying degrees and can be injected easily through microcatheters due to their slippery and compressible characteristics. The material was successfully used for embolization of 4 vascular intracranial tumours and 2 spinal vascular lesions in the cervical region, by superselective delivery. Histopathology confirmed absolute inertness of the microspheres.
Adult↗