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Biomedical subjects

A J Domb

Publications and source records attributed to A J Domb.

4 recordsLinked to original sources

Molecular weight changes in polymer erosion.

We report a study of the effects of polymer molecular weight on the erosion of polyanhydride copolymer matrices composed of 1,3-bis(p-carboxyphenoxy)-propane (CPP) and sebacic acid (SA) in aqueous solution. The erosion profile characteristically displays an induction period during which the erosion rate is relatively slow. The length of this period depends on the initial molecular weight of the polymer. The induction period may be characterized as a time during which a rapid decrease in polymer molecular weight occurs, the end of this period correlating with the time required for the polymer molecular weight to decrease to below a value of approximately 5000 (MW).

Decanoic Acids

Biodegradable polymers derived from amino acids.

This report describes general methods for the synthesis of biodegradable poly(amide anhydrides) and poly(amide esters) based on naturally occurring amino acids. The polymers were synthesized from dicarboxylic acids prepared by amidation of the amino group of an amino acid with a cyclic anhydride, or by amide coupling of two amino acids with a diacid chloride. This approach was demonstrated by the synthesis of polymers based on alanine and proline. Homo- and copolyanhydrides with sebacic acid of beta-alanyl succinamide, and N,N'-bis (beta-alanine)-1,3-benzene dicarboxamide, were synthesized by melt or solution polymerization. The copolymers prepared in solution had molecular weights up to 4500, while the copolymers prepared by melt condensation had higher molecular weights of about 30,000. Polymers were also prepared directly from the reaction of an amino acid and a diacid chloride. These polymers were soluble in dichloromethane and had molecular weights in the range 800-4800. A polyester of L-prolyl succinamide was prepared by melt condensation of the methyl ester derivative of the diacid and propylene glycol with acid catalysis. The polymer was transparent and pliable, and had a weight average molecular weight of 33,000. The poly(amide anhydrides) based on alanine and sebacic acid display a nearly linear degradation pattern with complete degradation in vitro after 5-10 d (phosphate buffer, pH 7.4 at 37 degrees C).

Amino Acids

Polyanhydrides. V. Branched polyanhydrides.

The objective of the present study was to investigate the properties of branched polyanhydrides and compare them to the corresponding linear polymers. Sebacic acid was polymerized with 1,3,5 benzenetricarboxylic acid and poly(acrylic acid) to yield random and graft-type branched polyanhydrides. The polymerization was followed until the gel point and the resulting polymers were evaluated for their physico-chemical properties and degradation behaviour. Drug release from these polymers was studied using morphine as a model drug. The experiment showed that the molecular weights of branched polyanhydride were significantly higher (mol wt 250,000) than the molecular weight of linear poly(sebacic anhydride) (mol wt 80,000). In the case of poly(acrylic acid) branched polymers, the molecular weight increased linearly with increasing concentration of poly(acrylic acid). The specific viscosities of the branched polyanhydrides were lower than linear polyanhydrides with similar molecular weights. Except for the difference in molecular weights, there were no noticeable changes in the physico-chemical or thermal properties of the branched polymers and the linear poly(sebacic anhydride). The degradation of the branched polyanhydride was triphasic and the degradation rates were faster than for linear poly(sebacic anhydride). The release of morphine from the branched polymers was lower than the corresponding poly(sebacic anhydride). Release of morphine was much higher from the poly(acrylic acid) branched polymers compared to the 1,3,5 benzenetricarboxylic acid branched polymers and increased with increasing concentrations of the branching agent. However, in both cases the release rates and the total amounts of morphine released approached that of poly(sebacic anhydride).

Anhydrides

Selective cell transplantation using bioabsorbable artificial polymers as matrices.

To date, selective cell transplantation has involved injecting cell suspensions into tissues or the vascular system. This study describes attaching cell preparations to bioerodable artificial polymers in cell culture and then implanting this polymer-cell scaffold into animals. Using standard techniques of cell harvest, single cells and clusters of fetal and adult rat and mouse hepatocytes, pancreatic islet cells, and small intestinal cells have been seeded onto biodegradable polymers of polyglactin 910, polyanhydrides, and polyorthoester. Sixty-five fetuses and 14 adult animals served as donors. One hundred fifteen polymer scaffolds were implanted into 70 recipient animals: 66 seeded with hepatocytes; 23 with intestinal cells and clusters; and 26 with pancreatic islet preparations. The cells remained viable in culture, and in the case of fetal intestine and fetal hepatocytes, appeared to proliferate while on the polymer. After four days in culture, the cell-polymer scaffolds were implanted into host animals, either in the omentum, the interscapular fat pad, or the mesentery. In three cases of fetal intestinal implantation coupled with partial hepatectomy, successful engraftment occurred in the omentum, one forming a visible 6.0 mm cyst. Three cases of hepatocyte implantation, one using adult cells and two using fetal cells, have also engrafted, showing viability of hepatocytes, mitotic figures, and vascularization of the cell mass. To date, no pancreatic islets have survived implantation. This method of cell transplantation, which we have termed "chimeric neomorphogenesis," is an alternative to current methods and requires further study.

Animals