In vivo characteristics of high molecular weight copoly(L-lactide/glycolide) with S-type degradation pattern for application in drug delivery systems.
Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates.
Fukuzaki
H
H
Department of Development, Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute.
Yoshida
M
M
Asano
M
M
Kumakura
M
M
Mashimo
T
T
Yuasa
H
H
Imai
K
K
Yamanaka
H
H
D000818:Animals; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D015918:Infusion Pumps, Implantable; D016729:Leuprolide; D008297:Male; D008970:Molecular Weight; D011098:Polyglactin 910 / Q000138:chemical synthesis / Q000737:chemistry*; D011467:Prostate / Q000187:drug effects; D051381:Rats
D003692:Delayed-Action Preparations; D007987:Gonadotropin-Releasing Hormone; D011098:Polyglactin 910; D016729:Leuprolide