Effect of ionic strength on the loading efficiency of model polypeptide/protein drugs in pH-/temperature-sensitive polymers.
In this report, the effect of ionic strength on the loading efficiency of three model polypeptide/protein drugs, namely angiotensin II, insulin, and cytochrome c, in pH- and temperature-sensitive terpolymers of poly(NIPAAm-co-butylmethacrylate-co-acrylic acid) (poly(NIPAAm-co-BMA-co-AA)) has been investigated. Loading efficiency of polypeptides in pH-/temperature-sensitive beads composed of poly(NIPAAm-co-BMA-co-AA) terpolymer is predominantly governed by hydrophobic interactions, both nonspecific surface interactions and/or specific interactions (binding pockets) between the protein and the polymer molecules. Thus, loading efficiency increases with ionic strength. However, as ionic strength increases further, polymer deswelling (collapse), which is also controlled by hydrophobic forces, becomes more pronounced, and consequently, a higher fraction of water is squeezed out during bead formation and the loading efficiency starts to decrease.
Ramkissoon-Ganorkar
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University of Utah, Department of Pharmaceutics and Pharmaceutical Chemistry/Center for Conrtrolled Chemical Delivery, Salt Lake City 84112, USA.
Baudys
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Kim
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SW
D000178:Acrylamides / Q000378:metabolism*; D000179:Acrylates / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D002417:Cattle; D003574:Cytochrome c Group / Q000378:metabolism; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D008689:Methacrylates / Q000378:metabolism*; D008970:Molecular Weight; D009994:Osmolar Concentration; D010455:Peptides / Q000378:metabolism*; D013696:Temperature
D000178:Acrylamides; D000179:Acrylates; D001672:Biocompatible Materials; D003574:Cytochrome c Group; D004337:Drug Carriers; D007328:Insulin; D008689:Methacrylates; C402664:NIPAAm-co-BMA-co-AA; D010455:Peptides; D000804:Angiotensin II