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Attachment of Mucin Specific Lectins to Alginate for Use as Bioadhesives

Published online by Cambridge University Press:  15 February 2011

Donald E. Chickering III ,
Jules S. Jacob ,
Annie Keung ,
Tejal A. Desai  and
Edith Mathiowitz
Donald E. Chickering III
Affiliation:
Brown University, Section of Artificial Organs, Biomaterials and Cellular Technology, Box G-B393, Providence, Rhode Island 02912
Jules S. Jacob
Affiliation:
Brown University, Section of Artificial Organs, Biomaterials and Cellular Technology, Box G-B393, Providence, Rhode Island 02912
Annie Keung
Affiliation:
Brown University, Section of Artificial Organs, Biomaterials and Cellular Technology, Box G-B393, Providence, Rhode Island 02912
Tejal A. Desai
Affiliation:
Brown University, Section of Artificial Organs, Biomaterials and Cellular Technology, Box G-B393, Providence, Rhode Island 02912
Edith Mathiowitz
Affiliation:
Brown University, Section of Artificial Organs, Biomaterials and Cellular Technology, Box G-B393, Providence, Rhode Island 02912
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Abstract

The use of bioadhesive materials for orally-delivered, controlled release systems could increase GI transit time and improve bioavailability. Through the covalent attachment of various ligands to drug delivery systems it is possible to engineer materials to adhere to specific moieties endogenous to the alimentary mucosal layer. The entire GI tract is covered by a continuous, protective, mucous coating made of 95% water and 5% electrolytes, lipids, proteins, and glycoproteins. The GI glycoproteins consist of a protein core with covalently attached carbohydrate side chains terminating in either L-fucose or sialic acid residues. There exist several plant and animal lectins which display high affinity binding to either of these sugars.

We have studied the effect on bioadhesion of attaching biotinylated Ulex Europaeus I (UEA-I), an L-fucose specific lectin derived from the gorse seed, to barium-loaded alginate microspheres. Two carbodiimidazole (CDI) coupling procedures were investigated: premicrosphere-fabrication coupling and post-microsphere-fabrication coupling. The attachment of lectin was confirmed using an ABC reaction with HRP staining. The pre-modified microspheres clearly showed better labeling than the post-modified. For in vivo assessment of bioadhesion, 3 cohorts of 4 rats were force fed slurries of control, pre- and post-modified microspheres in saline. The animals were X-rayed 1 hour after feeding and sacrificed 19 hours later. Their entire GI tracts were excised, X-rayed and the microsphere distribution was assessed. The premodified microspheres showed greater retention in all areas of the alimentary canal. The total percentage of microspheres remaining in the GI tract after 19 hours was: 18.6% post-modified and 37.1% pre-modified. These results correlate well with the intensity of the reaction seen with the HRP staining, and suggest that attachment of mucin specific ligands to polymer microspheres may improve bioadhesion.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 331: Symposium T – Biomaterials for Drug and Cell Delivery , 1993 , 67
Copyright
Copyright © Materials Research Society 1994

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