TY - JOUR
T1 - Chitosan-pentaglycine-phenylboronic acid conjugate
T2 - A potential colon-specific platform for calcitonin
AU - Smoum, Reem
AU - Rubinstein, Abraham
AU - Srebnik, Morris
PY - 2006
Y1 - 2006
N2 - Novel drug delivery vehicles based on the biodegradable, mucoadhesive polysaccharide chitosan covalently linked to a boronic acid protease inhibitor have been prepared and characterized. It was anticipated that these conjugates could protect a proteinaceous drug, such as salmon calcitonin, against proteolysis by serine proteases, an obstacle that prevents its oral administration. Specifically, 4-formylphenylboronic acid was linked to chitosan. Three types of conjugates were prepared. In the first, 4-formylphenylboronic acid was directly linked to chitosan. The other two conjugates employed glycylglycine and pentaglycine spacers. Enzyme-inhibition assays toward trypsin and elastase, in the presence of the enzyme chitosanase, demonstrated a strong inhibitory effect for the chitosan-pentaglycine-phenylboronic acid conjugates, while no inhibitory effect could be detected without chitosanase. The chitosan-pentaglycine-phenylboronic acid conjugate with the highest degree of substitution of 4-formyl-phenylboronic acid was able to decrease the salmon calcitonin degradation rate by trypsin. It is concluded that chitosan-pentaglycine-phenylboronic acid conjugates are a potential multifunctional, colon-specific vehicle for orally administered salmon calcitonin.
AB - Novel drug delivery vehicles based on the biodegradable, mucoadhesive polysaccharide chitosan covalently linked to a boronic acid protease inhibitor have been prepared and characterized. It was anticipated that these conjugates could protect a proteinaceous drug, such as salmon calcitonin, against proteolysis by serine proteases, an obstacle that prevents its oral administration. Specifically, 4-formylphenylboronic acid was linked to chitosan. Three types of conjugates were prepared. In the first, 4-formylphenylboronic acid was directly linked to chitosan. The other two conjugates employed glycylglycine and pentaglycine spacers. Enzyme-inhibition assays toward trypsin and elastase, in the presence of the enzyme chitosanase, demonstrated a strong inhibitory effect for the chitosan-pentaglycine-phenylboronic acid conjugates, while no inhibitory effect could be detected without chitosanase. The chitosan-pentaglycine-phenylboronic acid conjugate with the highest degree of substitution of 4-formyl-phenylboronic acid was able to decrease the salmon calcitonin degradation rate by trypsin. It is concluded that chitosan-pentaglycine-phenylboronic acid conjugates are a potential multifunctional, colon-specific vehicle for orally administered salmon calcitonin.
UR - http://www.scopus.com/inward/record.url?scp=33746671262&partnerID=8YFLogxK
U2 - 10.1021/bc050357y
DO - 10.1021/bc050357y
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C2 - 16848408
AN - SCOPUS:33746671262
SN - 1043-1802
VL - 17
SP - 1000
EP - 1007
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 4
ER -