Preparation of a copoly (dl-lactic/glycolic acid)-zinc oxide complex and its utilization to microcapsules containing recombinant human growth hormone.
A procedure to prepare a complex of copoly (dl-lactic/glycolic acid) and zinc oxide (PLGA-zinc oxide complex) was developed. Out of sparingly water-soluble zinc compounds, zinc oxide was most remarkably soluble in a PLGA/dichloromethane solution and the dissolution rates became faster as the water contents in the PLGA/dichloromethane solutions increased. Since the solubility of zinc oxide was saturated at approximately 0.5-fold molar ratio to PLGA and water was generated with dissolution of zinc oxide in the PLGA/dichloromethane solutions, it is suggested that zinc oxide interacts with the terminal carboxyl group of PLGA. In addition, the glass-transition temperature of a solid material obtained by vacuum-drying the PLGA/dichloromethane solution dissolving zinc oxide became higher as the zinc content increased, suggesting that the formation of a PLGA-zinc oxide complex. Microcapsules were prepared with the PLGA-zinc oxide complex using recombinant human growth hormone (rhGH) in order to evaluate an effect of the complex on protein release and stability of protein in the microcapsules. Released rhGH amount from the microcapsules prepared with the PLGA-zinc oxide complex after subcutaneous administration in rats was significantly larger than that from microcapsules prepared with PLGA alone, indicating that rhGH molecules in the microcapsules was stabilized by the PLGA-zinc oxide complex.
Yamagata
Yutaka
Y
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, 17-85 Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. Yamagata_Yutaka@takeda.co.jp
Misaki
Masafumi
M
Kurokawa
Tomofumi
T
Taira
Keiko
K
Takada
Shigeyuki
S
D000818:Animals; D002214:Capsules; D019382:Human Growth Hormone / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D011100:Polyglycolic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012995:Solubility; D015034:Zinc Oxide / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D002214:Capsules; D011108:Polymers; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015034:Zinc Oxide