Deterioration of polyamino acid-coated alginate microcapsules in vivo.

Deterioration of polyamino acid-coated alginate microcapsules in vivo. Research Abstract Details 

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Deterioration of polyamino acid-coated alginate microcapsules in vivo. Abstract Text:

J M van Raamsdonk,R M Cornelius,J L Brash,P L Chang,

The implantation of immuno-isolated recombinant cell lines secreting a therapeutic protein in alginate microcapsules presents an alternative approach to gene therapy. Its clinical efficacy has recently been demonstrated in treating several genetic diseases in murine models. However, its application to humans will depend on the long-term structural stability of the microcapsules. Based on previous implantations in canines, it appears that survival of alginate-poly-L-lysine-alginate microcapsules in such large animals is short-lived. This article reports on the biological factors that may have contributed to the degradation of these microcapsules after implantation in dogs. Alginate microcapsules coated with poly-L-lysine or poly-L-arginine were implanted in subcutaneous or intraperitoneal sites. The retrieved microcapsules showed a loss of mechanical stability, as measured by resistance to osmotic stress. The polyamino acid coats were rendered fragile and easily lost, particularly when poly-L-lysine was used for coating and the intraperitoneal site was used for implantation. Various plasma proteins were associated with the retrieved microcapsules and identified with western blotting to include Factor XI, Factor XII, prekallikrein, HMWK, fibrinogen, plasminogen, ATIII, transferrin, alpha-1-antitrypsin, fibronectin, IgG, alpha-2-macroglobulin, vitronectin, prothrombin, apolipoprotein A1, and particularly albumin, a major Ca-transporting plasma protein. Complement proteins (C3, Factor B, Factor H, Factor I) and C3 activation fragments were detected. Release of the amino acids from the microcapsule polyamino acid coats was observed after incubation with plasma. indicating the occurrence of proteolytic degradation. Hence, the loss of long-term stability of the polyamino acid-coated alginate microcapsules is associated with activation of the complement system, degradation of the polyamino acid coating, and destabilization of the alginate core matrix, probably through loss of calcium-mediated ionic cross-linking of the guluronic acid polymers in the alginate. These destructive forces may be slightly mitigated by using poly-L-arginine instead of poly-L-lysine for coating and by implanting in a subcutaneous instead of an intraperitoneal site. However, the long-term stability of such devices may require significant improvements in the microcapsule polymer chemistry to withstand such biological impediments.

Deterioration of polyamino acid-coated alginate microcapsules in vivo. Publishing Authors By Initials

JM van Raamsdonk,RM Cornelius,JL Brash,PL Chang,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research

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Deterioration of polyamino acid-coated alginate microcapsules in vivo. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biomaterials science. Polymer edition

VOLUME: 13

Page Numbers: 863-84

Journal Abbreviation:

ISSN: 0920-5063

DAY: 20

MONTH: 02

YEAR: 2002

Deterioration of polyamino acid-coated alginate microcapsules in vivo. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9007393

Deterioration of polyamino acid-coated alginate microcapsules in vivo. Keywords Mesh Terms:

KEYWORDS: Protein Binding

MESH TERMS: chemistry

Chemical & Substance for Abstract: Deterioration of polyamino acid-coated alginate microcapsules in vivo. Information

Substance Name: alginic acid

Registry Number: 9005-32-7

Grant and Affiliation Information for Deterioration of polyamino acid-coated alginate microcapsules in vivo.

AFFILIATION: Department of Medical Sciences, Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.

Country: Netherlands

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MEDLINETA: J Biomater Sci Polym Ed

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