Trypsin inhibition, calcium and zinc ion binding of starch-g-poly(acrylic acid) copolymers and starch/poly (acrylic acid) mixtures for peroral peptide drug delivery

Newly synthesised starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures were evaluated for their in vitro inhibition potency towards the proteolytic enzyme trypsin. Their Ca2+ and Zn2+ binding capacity was measured. Carbopol((R)) 934P was used as reference polymer. Starch-g-poly(acrylic acid) copolymers were prepared by chemical grafting and Co-60 irradiation, the starch/poly(acrylic acid) mixtures by freeze-drying. The influence of preparation method, the ratio starch:acrylic acid, the neutralisation degree and for the freeze-dried polymers the influence of heat treatment after freeze-drying was investigated. All freeze-dried polymers showed a higher inhibition factor (IF) than the chemically grafted and Co-60 irradiated starches, which all showed significantly lower IF than Carbopol((R)) 934P. The heat treated freeze-dried polymer Amioca((R))/poly(acrylic acid) (1: 1) showed a significantly higher IF than the reference polymer (Mann-Whitney test, p <0.05). The Ca2+ and Zn2+ binding capacity of all chemically grafted starches was much lower than for Carbopol((R)) 934P. Only the Co-60 irradiated starches and freeze-dried polymers with ratio 1:3 approached the binding capacity of the reference polymer. The freeze-dried polymers showed the highest proteolytic enzyme inhibition potency. Freeze-drying and Co-60 irradiation could result in the highest ion binding capacity. This combination of proteolytic enzyme inhibition activity and ion binding capacity makes these polymers hopeful excipients for successful oral peptide delivery. (C) 2001 Elsevier Science B.V. All rights reserved.