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Biomedical subjects

M F Goosen

Publications and source records attributed to M F Goosen.

At least 19 recordsLinked to original sources
PubMed1999

Physico-chemical and mass transfer considerations in microencapsulation.

To gain better insight into mass transfer problems in encapsulated cell systems requires a combination of experimental investigations and mathematical modeling. Specific mass transfer studies are reviewed including oxygen transfer in immobilized animal cell culture bioreactors, modeling of polymer droplet formation and encapsulated animal cell growth, and growth of somatic tissue encapsulated in alginate using electrostatics. Special emphasis is given to electrostatic droplet generation for cell immobilization.

Alginates↗
PubMed1996

Role of polymers in improving the results of stenting in coronary arteries.

This article is a review of recent developments of polymer-related stents mainly employed in the coronary arteries, including polymer-coated stents, biostable stents and biodegradable stents. Polymer paving is covered as well. The problems with the stents currently investigated and the development of new stents are discussed.

Adsorption↗
PubMed1995

Mathematical modelling of immobilized animal cell growth.

A two-dimensional mathematical model for animal cell growth was employed to study the suspension, as well as stationary, culture of micro-encapsulated and gel immobilized animal cells. For stationary microcapsules with low-viscosity intracapsular liquid, it was found that capsule radius, capsule loading and medium-change time have the most significant effects on the intracapsular cell density. The model was also adapted to simulate other scenarios of cell growth such as in gel beads and suspended microcapsules. The simulated time course of oxygen concentration and specific growth rate revealed a complicated interaction between material transport and cell growth kinetics. With the mass transfer coefficient for oxygen transfer (KLa') into the medium equal to 4.0 hr-1, for instance, it was found that the specific growth rate of the microencapsulated cells was controlled by the supply of glucose and oxygen. When the value of KLa' was reduced to 0.6 hr-1, however, oxygen supply appeared to be the sole factor affecting the specific growth rate. In the case of suspended gel beads, a simulation revealed a higher cell density towards the gel bead surface. The transport of nutrients and oxygen to the central region of the gel bead was apparently blocked by the surrounding cells.

Animals↗
PubMed1994

Controlled release of albumin from chitosan-alginate microcapsules.

A polymeric delayed-release protein delivery system was investigated with albumin as a model drug. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Variables believed to be important for membrane formation were examined; these included reaction time, chitosan molecular weight, alginate concentration, chitosan concentration, and solution pH. An alginate-chitosan reaction time, in the range of 10 to 45 min, had no effect on the release of albumin. Increasing the alginate concentration, however, resulted in a decreased rate of release of albumin (from 37% release at 4 h with 1.5% alginate to 20% release with 2.5% alginate). Another key variable was the chitosan molecular weight. The molecular weight of chitosan was varied from 1.25 x 10(6) to 0.25 x 10(6) through a nitrite oxidation reaction with sodium nitrite. Decreasing the molecular weight increased the release of albumin (from 37% release at 4 h with high molecular weight chitosan to 77% release with low molecular weight chitosan). The pH of the extracapsular environment was found to affect the release of albumin significantly (15% release over 24 h at a pH 3.0 and 73% release at pH 8.0). Capsules produced with high molecular weight chitosan and a combination of high and low molecular weight chitosan gave the best results for reducing elution of albumin in the first 4 h and increasing elution in the following 20 h.

Albumins↗
PubMed1994

Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties.

Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol. wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol. wt poly(D,L-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗
PubMed1993

Polysaccharide microcapsules and macroporous beads for enhanced chromatographic separation.

One recent solution to the diffusion problem found in conventional chromatographic separation is the use of dual porosity beads in which large pores allow for convective flow and smaller pores allow for molecular diffusion. In our studies, dual porosity beads were prepared from carrageenan using an emulsion method. Effects of polymer type, polymer concentration, toluene content, gelling temperature, and stirring speed on the structure of porous beads were investigated. In an alternative approach, one of the interacting molecules in affinity chromatography, can be entrapped within semipermeable microcapsules. This has the advantage of increased adsorption capacities. Using blue dextran and albumin as a model system, alginate-chitosan capsules, containing blue dextran, were employed in the recovery of albumin from a saline solution.

Alginates↗
PubMed1992

Recombinant protein production in insect cell cultures infected with a temperature-sensitive baculovirus.

Spodoptera frugiperda (IPLB-SF-21) insect cells were grown in shake-flasks and infected with a temperature-sensitive baculovirus to express the gene of chloramphenicol acetyl transferase (CAT) in serum-free medium (SF-900) and two serum-supplemented media (IPL-41 and Grace's). In temperature-shift experiments (cell growth at 33 degrees C followed by virus replication at 27 degrees C 3-4 days later), virus and CAT production were much poorer in the serum-free medium than in serum-supplemented media, though cell growth was virtually the same in the different media tested. In all the three media, highest virus and CAT titers were obtained at the lowest MOI (multiplicity of infection 0.02). This result is contrary to that obtained in constant-temperature culture (27 degrees C for both cell growth and virus replication). Virus and CAT production was greatly improved when the entire culture was run at constant temperature. It appeared that infected cells were severely damaged at 33 degrees C (6 degrees C above the optimal 27 degrees C), resulting in little or no virus and protein production. As a result of these temperature-shift experiments, a larger-scale (14 1 air-lift bioreactor) serum-free culture of Sf-9 insect cells was conducted at constant temperature (27 degrees C) to produce recombinant protein (beta-galactosidase). A cell density as high as 1 x 10(7) cells.ml-1, and a beta-gal concentration of up to 104,000 unit.ml-1 were achieved.

Animals↗
PubMed1992

Large-scale insect cell culture.

Significant advances have been made over the past year in our understanding of the protective mechanisms, both fluid-mechanical and biological, of media additives on suspended animal cells. The degree of protection offered by different additives, such as pluronic polyol, appears to be cell-type dependent, varying quite dramatically not only between insect and mammalian cells, but also between different insect cell lines themselves.

Animals↗
PubMed1991

Large-scale insect cell culture: methods, applications and products.

The primary development in large-scale insect cell culture over the past year has been the continuing accumulation of documented evidence (fundamental and applied) that conventional aerated stirred-tank and air-lift bioreactors may be employed for insect cell cultivation and recombinant protein production, provided that air sparging, agitation, and the addition to the medium of Pluronic F-68 and methyl cellulose polymers are carefully controlled.

Animals↗
PubMed1990

Kinetics of protein diffusion from a poly(D,L-lactide) reservoir system.

The release kinetics of albumin diffusion from a poly(D,L-lactide) reservoir system was investigated with the long-term aim of developing a multidose pulsatile delivery system. Albumin pellets were coated with polylactide of varying viscosity-average molecular weight, Mv, and concentration, and incubated in aqueous solution. The albumin release profile was approximated by zero-order release kinetics, with release rates ranging from 3 to 1800 mg/day. The permeability of the poly(D,L-lactide) membranes to albumin diffusion ranged from 1 x 10(-9) to 100 x 10(-9) cm2/S, and was found to decrease with increasing membrane thickness (18 to 1400 microns) and density (300 to 3000 mg/cm3). The initiation of albumin release from the pellets could be delayed from a few hours to more than one month by increasing the Mv of the polylactide from 6.2 x 10(3) to 140 x 10(3) and raising the concentration of the polymer coating solution from 50 to 100 mg/mL. The diversity in delayed-release effect and the variations in membrane permeabilities were attributed to changes in membrane porosity and polymer morphology.

Albumins↗
PubMed1987

Microencapsulated cells as hormone delivery systems.

Transplantation of pancreatic islets of Langerhans has been shown to prevent the development of many of the complications associated with diabetes. Transplanted islets, however, are readily rejected by the immune system. The use of artificial membranes to isolate the transplanted islets from the immune system of the host prolongs islet allografts in experimental animals. We have developed a method for encapsulating islets in semipermeable membranes composed of alginate and polylysine. The same technique can be applied to other endocrine cell types. The capsules are 700 to 800 micron in diameter with a hydrogel membrane approximately 4 micron thick. Intraperitoneal allografts of 5 x 10(3) encapsulated islets reversed diabetes in rats for up to 21 months and intact capsules with viable beta cells could be recovered from the recipients. Microencapsulation of endocrine cells for transplantation could potentially be used in the clinical treatment of hormone deficiency diseases.

Animals↗
PubMed1984

Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane.

Prolonged survival of islet allografts in streptozotocin-induced diabetic rats was achieved by encapsulating individual islets in protective, biocompatible alginate-polylysine-alginate membranes. A single intraperitoneal transplant of encapsulated islets reversed the diabetic state for up to 1 year. In contrast, a single injection of unencapsulated islets was effective for less than 2 weeks. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential in the treatment of diseases requiring organ transplantation, such as diabetes and liver disease.

Alginates↗
PubMed1984

Injectable microencapsulated islet cells as a bioartificial pancreas.

Rat islets encapsulated in semipermeable membranes remained viable in culture for 4 months. Multiple allotransplants of islets encapsulated in alginate-polylysine-polyethyleneimine membranes restored normoglycemia in recipient diabetic rats for most of a 90-day experimental period. Each individual transplant restored normal fasting plasma glucose levels for 15-20 d. The failure of the encapsulated islets was caused by an inflammatory response induced by polyethyleneimine. In contrast a single transplant of islets encapsulated in a biocompatible alginate-polylysine-alginate membrane restored normoglycemia in recipient animals for up to 10 months. Capsules with intact membranes and containing viable islets were recovered from the abdominal cavity 5 months post-transplantation. SEM studies on capsule membranes revealed essentially smooth surfaces. Differences between wet and dry wall thicknesses indicated that the membrane is a hydrogel, 4.00 +/- 0.28 micron thick in an aqueous environment. The clinical potential of transplanting cells encapsulated in biocompatible semipermeable hydrogel membranes is demonstrated by this study.

Animals↗
PubMed1983

Properties of a heparin-poly(vinyl alcohol) hydrogel coating.

Some physical, chemical, and biological characteristics of a heparin-PVA hydrogel potentially useful as a thromboresistant coating for the preparation of small-diameter vascular prostheses and blood-sampling catheters have been determined. The molecular weight between crosslinks in the acetal crosslinked gel was approximately 8000, permitting proteins the size of albumin to enter the interior of the gel. The release rate of heparin from a gel containing 7 mg/g gel was 10(-2) micrograms/g min which was significantly lower than the reported minimum required for thromboresistance of ionically heparinized materials. Nevertheless, in vitro biological activity was observed in both thrombin time and plasma recalcification time assays, which could not be attributed to the release of heparin into the incubated plasma. Correlation of final heparin contents with the amount of terminal amino acid residues in three samples of heparin suggests that the heparin is bound to the PVA in the gel through the amino acid terminus; this provides a plausible explanation for the retention of biological activity by the immobilized heparin.

Animals↗
PubMed1983

Microencapsulation of crystalline insulin or islets of Langerhans: an insulin diffusion study.

Microcapsules containing insulin crystals or islets of Langerhans were made by extruding a mixture of insulin crystals or islets and sodium alginate into a calcium chloride solution, and then coating it with poly-l-lysine. When these microcapsules were incubated at 37 degrees C, insulin could be detected readily in the medium, indicating that the microcapsular membrane is permeable to insulin. The efficiency of insulin encapsulation with crystalline insulin declined as the concentration in the sodium alginate mixture increased. Over 90% of the entrapped insulin was released after 3 days of incubation at 37 degrees C, indicating that the rate of insulin release from the microcapsules requires modification if the microcapsules are to be used as a long-term insulin delivery system. The amount of insulin secreted by the encapsulated islets was not significantly different from that of unencapsulated islets, suggesting the islets were not affected by the modified encapsulation process.

Alginates↗
PubMed1983

Slow release of insulin from a biodegradable matrix implanted in diabetic rats.

This report describes the development of a long-acting insulin accomplished by the slow release of hormone from an implantable, biodegradable matrix. Rats made diabetic with streptozotocin received a single subcutaneous implant of insulin-albumin microbeads that released biologically active insulin for periods up to 3 wk. The mean fasting blood glucose level for treated animals was 88 mg/dl as compared with 392 mg/dl for untreated diabetic controls. With a mean starting body weight of 187 g, treated animals gained weight reaching a mean weight of 228 g; in contrast, untreated animals lost weight to a mean of 175 g. When insulin-albumin microbeads were periodically implanted and removed, lower blood glucose levels were only associated with the presence of the implants. The microbead implants biodegraded in 4-8 wk, thus obviating the need for surgical removal. These results suggest that a long-acting insulin may be produced by the entrapment of insulin within a biodegradable matrix.

Animals↗