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 t hree model polypeptide/protein drugs, namely angiotensin II, insulin, and c ytochrome c, in pH- and temperature sensitive terpolymers of poly(NIPAAm-co -butylmethacrylate-co-acrylic acid) (poly(NIPAAm-co-BMA-ca-AA)) has been in vestigated. Loading efficiency of polypeptides in pH-/temperature-sensitive beads composed of poly(NIPAAm-co-BMA-co-AA) terpolymer is predominantly go verned by hydrophobic interactions, both nonspecific surface interactions a nd/or specific interactions (binding pockets) between the protein and the p olymer molecules. Thus, loading efficiency increases with ionic strength. H owever, as ionic strength increases further, polymer deswelling (collapse), which is also controlled by hydrophobic forces, becomes more pronounced, a nd consequently, a higher fraction of water is squeezed out during bead for mation and the loading efficiency starts to decrease.