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Abstract
There are a variety of both natural and synthetic polymeric systems that have been
investigated for the controlled release of proteins. Many of the procedures employed
to incorporate proteins into a polymeric matrix can be harsh and often cause denaturation
of the active agent. Alginate, a naturally occurring biopolymer extracted from brown
algae (kelp), has several unique properties that have enabled it to be used as a matrix
for the entrapment and/or delivery of a variety of biological agents. Alginate polymers
are a family of linear unbranched polysaccharides which contain varying amounts of
1,4'-linked beta-D-mannuronic acid and alpha-L-guluronic acid residues. The residues
may vary widely in composition and sequence and are arranged in a pattern of blocks
along the chain. Alginate can be ionically crosslinked by the addition of divalent
cations in aqueous solution. The relatively mild gelation process has enabled not
only proteins, but cells and DNA to be incorporated into alginate matrices with retention
of full biological activity. Furthermore, by selection of the type of alginate and
coating agent, the pore size, degradation rate, and ultimately release kinetics can
be controlled. Gels of different morphologies can be prepared including large block
matrices, large beads (>1 mm in diameter) and microbeads (<0.2 mm in diameter). In
situ gelling systems have also been made by the application of alginate to the cornea,
or on the surfaces of wounds. Alginate is a bioadhesive polymer which can be advantageous
for the site specific delivery to mucosal tissues. All of these properties, in addition
to the nonimmunogenicity of alginate, have led to an increased use of this polymer
as a protein delivery system. This review will discuss the chemistry of alginate,
its gelation mechanisms, and the physical properties of alginate gels. Emphasis will
be placed on applications in which biomolecules have been incorporated into and released
from alginate systems.