Prostaglandin releasing polymers - stability and efficacy.

In summary, PGI2 is approximately 3 orders of magnitude more potent than PGE1 in the prevention of platelet aggregation. Similarly PGE1 is an order of magnitude more potent than PGD2 (ID50's = 5.3 x 10(-10) M, 1.3 x 10(-7) M and 1.4 x 10(-6) M for PGI2, PGE1 and PGD2 respectively). Results from biological and infrared stability studies demonstrate that both PGI2 and PGE1 are stable for extended periods of time when dispersed within hydrophobic polymer matrices, an important consideration in the design of nonthrombogenic, prostaglandin controlled release polymers. Finally, both PGE1 and PGI2 controlled release polymers inhibit platelet aggregation in contacting blood, of which PGE1 produced greater platelet aggregation inhibition (90% inhibition) than did PGI2 (75% inhibition). However, PGE1 controlled release polymers significantly reduced platelet adhesion (11.25 +/- 3.68 platelets/mm2) compared to control polymers (50.65 +/- 8.8 platelets/mm2) while PGI2 controlled release polymers demonstrated no improvement in platelet adhesion (25.00 +/- 18.61 platelets/mm2) relative to control polymers (30.43 +/- 7.62 platelets/mm2). One cannot conclude that the lack of reduced platelet adhesion on the PGI2 controlled release surfaces is due to the instability of PGI2. The fact that significant inhibition of platelet aggregation in both blood fractions which contacted the PGI2 controlled release surfaces occurred substantiates that the released PGI2 was active. It must be concluded that PGI2 does not affect platelet adhesion. It is interesting to note that less platelets adhered to the PGI2 control PVC surfaces than on the PGE1 control PVC surfaces. The PGI2 control PVC surfaces were equilibrated with a TRIZMA buffer in 5% dextrose (to provide isotonicity) while the PGE1 control PVC surfaces were equilibrated in isotonic phosphate buffer saline.