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

• Published in: Journal of controlled release Vol. 75; no. 3; pp. 357 - 364
• Main Authors: Ameye, D, Voorspoels, J, Foreman, P, Tsai, J, Richardson, P, Geresh, S, Remon, J.P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.08.2001; Elsevier
• Subjects: Acrylic Resins - administration & dosage; Administration, Oral; Biological and medical sciences; calcium; Calcium - metabolism; Calcium and zinc ion binding; Drug Delivery Systems; General pharmacology; Medical sciences; Oral peptide delivery; Peptides - administration & dosage; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; poly(acrylic acid); starch; Starch - administration & dosage; Starch/poly(acrylic acid) mixtures; Starch– g-poly(acrylic acid) copolymers; Trypsin inhibition; Trypsin Inhibitors - administration & dosage; zinc; Zinc - metabolism; Trypsin inhibition; Starch– g-poly(acrylic acid) copolymers; Calcium and zinc ion binding; Oral peptide delivery; Starch/poly(acrylic acid) mixtures; Delivery system; Acrylic acid copolymer; Pharmaceutical technology; Serine endopeptidases; Peptides; Enzyme; Starch; Oral administration; Zinc Cations; Peptidases; Biological fixation; Trypsin; Acrylic acid polymer; Dosage form; Hydrolases; Inhibition; Calcium Cations
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(01)00408-4

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 Ca 2+ and Zn 2+ binding capacity was measured. Carbopol ® 934P was used as reference polymer. Starch– g-poly(acrylic acid) copolymers were prepared by chemical grafting and 60Co 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 60Co irradiated starches, which all showed significantly lower IF than Carbopol ® 934P. The heat treated freeze–dried polymer Amioca ®/poly(acrylic acid) (1:1) showed a significantly higher IF than the reference polymer (Mann–Whitney test, p<0.05). The Ca 2+ and Zn 2+ binding capacity of all chemically grafted starches was much lower than for Carbopol ® 934P. Only the 60Co 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 60Co 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.