In vivo characteristics of low molecular weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers for drug delivery systems.
Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.
Department of Development, Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Gumma, Japan.
H
H
Fukuzaki
M
M
Yoshida
M
M
Asano
M
M
Kumakura
T
T
Mashimo
H
H
Yuasa
K
K
Imai
H
H
Yamanaka
D000818:Animals; D001673:Biodegradation, Environmental; D004343:Drug Implants / Q000737:chemistry*; D006880:Hydroxy Acids / Q000737:chemistry*; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry*; D019344:Lactic Acid; D008297:Male; D008970:Molecular Weight; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains
D004343:Drug Implants; D006880:Hydroxy Acids; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)