Biomedical subjects

E Mathiowitz

Publications and source records attributed to E Mathiowitz.

7 recordsLinked to original sources

PubMed1991

Controlled and modulated release of basic fibroblast growth factor.

Basic fibroblast growth factor has multivariate effects in stimulating cell growth and the processes that surround tissue repair. Pathophysiologic studies have been hampered by the stability of the compound. Though very potent, basic fibroblast growth factor is rapidly degraded when injected or ingested. Controlled release of basic fibroblast growth factor would allow for examination of the chronic effects of this compound. Conventional matrix polymer-based release devices were fabricated and basic fibroblast growth factor released in a sustained fashion, but 99% of basic fibroblast growth factor mitogenic activity was lost. The source of these losses was identified and preventative measures examined. Preservation and stabilization of basic fibroblast growth factor was accomplished by binding the factor to heparin-Sepharose beads. This permitted prolonged storage, repeated handling, and the encapsulation of basic fibroblast growth factor within a microspherical controlled-release device using a naturally occurring polymer material, alginate. Encapsulation was accomplished with 77% efficiency and 87.5 +/- 12% of the basic fibroblast growth factor was released in a biologically active form. Release activation and regulation was achieved when cleavage of the basic fibroblast growth factor-heparin bonds was enhanced (e.g. by enzymatic bond cleavage with heparinase). Kinetic profiles were identified for a variety of experimental conditions and the effects of the controlled release of basic fibroblast growth factor on BALBc/3T3 fibroblasts examined.

Alginates↗

PubMed1991

A novel, self-correcting membrane coating technique.

A novel coating process, leading to formation of uniform, defect-free coating on solid dosage forms, is proposed. The coating process, termed "diffusion-controlled interfacial complexation," involves a chemical reaction between a reactant incorporated in the solid unit to be coated and a polymer solution, forming the coating medium. The reaction results in the formation of an insoluble reactant-polymer film around the solid. The rate of film/membrane formation is controlled by the rate of diffusion of reactant through the reactant-polymer film. In the model system, calcium acetate was selected as the reactant and algin as the polymer. The coating process was mathematically characterized in terms of rate of increase in film thickness, film weight, and depletion of reactant. Compressed tablets coated using the above process provided zero-order release in distilled water.

Dosage Forms↗

PubMed1990

Morphology of polyanhydride microsphere delivery systems.

Scanning electron microscopy (SEM) was used to elucidate the mechanism of polymer degradation and drug release in polyanhydride microspheres. Three different fabrication methods--solvent removal, solvent evaporation, and hot melt microencapsulation--were used to prepare polyanhydride microspheres containing a variety of drugs. The morphology of these microspheres releasing drug in vitro and in vivo was studied by SEM and compared with degradation and release data measured by conventional methods. Microspheres prepared by the three techniques were shown to have distinctive morphological characteristics induced by the nature of the fabrication method. In addition, SEM analysis could be used to explain the drug release profiles and polymer degradation behavior seen in vitro as well as the in vivo effects of insulin-loaded microspheres on diabetic rats. This study has shown SEM to be an important and powerful tool for analyzing the effects of microsphere fabrication method on drug release.

Anhydrides↗

PubMed1989

Intracerebral drug delivery in rats with lesion-induced memory deficits.

Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p less than 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

Anhydrides↗

PubMed1988

Polyanhydride microsphere formulation by solvent extraction.

A novel process based on solvent extraction was developed to produce drug-loaded polyanhydride microspheres for controlled-release applications. The technique consists of adding a chloroform solution of polyanhydride and drug into a stirred silicone oil phase containing suspended droplets of surfactant. No chemical reaction, heating, nor contact with water was required in this process. The microspheres produced were capable of releasing various dyes for prolonged periods of time.

Anhydrides↗

PubMed1988

Enzymatically controlled drug delivery.

An approach for providing feedback control for polypeptide drugs in a polymeric controlled-release system uses a trigger molecule and a polymer-bound enzyme that, in the presence of that trigger molecule, will cause an acid or a base to form. When the pH inside the polymer system changes, the solubility of the drug shifts dramatically, which changes the diffusion or dissolution driving force, and hence the release rate changes correspondingly. This concept was tested using a controlled-release system of ethylene/vinyl acetate copolymer containing insulin and immobilized glucose oxidase. The enzymatic reaction of glucose to gluconic acid reduces the pH in the polymer microenvironment. Since insulin solubility increases with decreasing pH (at physiologic pH, this is true for an insulin with an isoelectric point of 7.4 or higher), the release of insulin increases in response to glucose concentration. The feasibility of this concept has been shown using trilysyl insulin with an isoelectric point of 7.4. Multiple exposures to buffered glucose solutions over several weeks caused insulin release to reversibly increase during each exposure. Polymer-implanted diabetic rats infused with glucose solutions showed a significant increase in insulin concentration in 30 min-an effect not observed in three different sets of control rats.

Animals↗

PubMed1986

Polyanhydrides for controlled release of bioactive agents.

This report is a review of the development of a drug delivery system based on biorodible polyanhydrides. With the water labile anhydride linkage, a wide range of matrix degradation and drug release rates can be obtained from these drug-carriers. In addition to monolithic formulations, the feasibility of an injectable system by microencapsulation is demonstrated. The possibility of enhancing the release externally by an ultrasonic source has also been explored. The polymers tested showed good tissue biocompatibility and their breakdown products showed no adverse toxicological effects. Preliminary in vivo results confirmed the efficacy of these devices.

Anhydrides↗