Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin.
Insulin (Ins) spontaneously and easily complexed with the hydrogel nanoparticle of hydrophobized cholesterol-bearing pullulan (CHP) in water. The complexed nanoparticles (diameter 20-30 nm) thus obtained formed a very stable colloid. The thermal denaturation and subsequent aggregation of Ins were effectively suppressed upon complexation. The complexed Ins was significantly protected from enzymatic degradation. Spontaneous dissociation of Ins from the complex was barely observed, except in the presence of bovine serum albumin. The original physiological activity of complexed Ins was preserved in vivo after i.v. injection.
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Japan.
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K
Akiyoshi
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Kobayashi
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Shichibe
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Mix
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Baudys
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Kim
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J
Sunamoto
D000818:Animals; D002784:Cholesterol / Q000737:chemistry*; D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000737:chemistry; D002942:Circular Dichroism; D003102:Colloids; D004337:Drug Carriers; D004355:Drug Stability; D005936:Glucans / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D003102:Colloids; D004337:Drug Carriers; D005936:Glucans; D007004:Hypoglycemic Agents; D007328:Insulin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C009109:pullulan; D002784:Cholesterol; D002918:Chymotrypsin