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(ac rylic acid) mixtures were evaluated for their in vitro inhibition potency t owards the proteolytic enzyme trypsin. Their Ca2+ and Zn2+ binding capacity was measured. Carbopol((R)) 934P was used as reference polymer. Starch-g-p oly(acrylic acid) copolymers were prepared by chemical grafting and Co-60 i rradiation, the starch/poly(acrylic acid) mixtures by freeze-drying. The in fluence of preparation method, the ratio starch:acrylic acid, the neutralis ation degree and for the freeze-dried polymers the influence of heat treatm ent after freeze-drying was investigated. All freeze-dried polymers showed a higher inhibition factor (IF) than the chemically grafted and Co-60 irrad iated 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-Wh itney 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 th e binding capacity of the reference polymer. The freeze-dried polymers show ed the highest proteolytic enzyme inhibition potency. Freeze-drying and Co- 60 irradiation could result in the highest ion binding capacity. This combi nation of proteolytic enzyme inhibition activity and ion binding capacity m akes these polymers hopeful excipients for successful oral peptide delivery . (C) 2001 Elsevier Science B.V. All rights reserved.