TY - JOUR
T1 - 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
AU - Ameye, D.
AU - Voorspoels, J.
AU - Foreman, P.
AU - Tsai, J.
AU - Richardson, P.
AU - Geresh, S.
AU - Remon, J. P.
PY - 2001/8/10
Y1 - 2001/8/10
N2 - 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® 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 Ca2+ and Zn2+ 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.
AB - 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® 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 Ca2+ and Zn2+ 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.
KW - Calcium and zinc ion binding
KW - Oral peptide delivery
KW - Starch-g-poly(acrylic acid) copolymers
KW - Starch/poly(acrylic acid) mixtures
KW - Trypsin inhibition
UR - http://www.scopus.com/inward/record.url?scp=0035839209&partnerID=8YFLogxK
U2 - 10.1016/S0168-3659(01)00408-4
DO - 10.1016/S0168-3659(01)00408-4
M3 - Article
C2 - 11489322
AN - SCOPUS:0035839209
SN - 0168-3659
VL - 75
SP - 357
EP - 364
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -