title: A new animal model for evaluation of long-term growth rate over one month by rhGH/PLGA microcapsule formulations.
abstract: A new animal model to evaluate the long-term growth rate produced by a sustained-release formulation of recombinant human growth hormone (rhGH) over one month was developed and the usefulness of our microcapsule formulations was demonstrated in this model. Long-term pharmacological effects by subcutaneous injection of microcapsules for sustained release of rhGH were evaluated in hypophysectomized (Hpx) rats treated with immunosuppressive agent along with hormone supplement. Copoly(DL-lactic/glycolic)acid (PLGA) microcapsules for sustained release of rhGH, a two-week sustained-release formulation (rhGH-SR-2W) and a one-month sustained-release formulation (rhGH-SR-1M), were prepared by a solid-in-oil-in-water emulsion solvent evaporation technique. Body-weight gain, body-length gain and serum levels of rat insulin-like growth factor-I (rIGF-I) induced by subcutaneous injection of rhGH-SR were compared with those by daily injections of rhGH solution in Hpx rats for 35 days. Serum IGF-I levels in Hpx rats after the injection of rhGH-SR2W microcapsules were higher than those after daily injections of rhGH solution. Body-length gain, a new parameter, after single injection of rhGH-SR-1M microcapsules demonstrated the higher growth rate than that after daily injections of rhGH solution for 35 days. Thus, single injection of rhGH-SR microcapsules demonstrated long-term pharmacological effects greater than those by daily injections of rhGH solution in a newly developed model, immunosuppressed Hpx rats.
authors.affiliation: Drug Formulation Research Laboratories, Takeda Chemical Industries, Ltd, 2-17-85, Juso-honmachi, Yodogawa-ku, Osaka 532-8686, Japan. Takada_Shigeyuki@takeda.co.jp
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Takada
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Misaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Taira
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002214:Capsules; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003692:Delayed-Action Preparations; D005260:Female; D006128:Growth / Q000187:drug effects*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry*; D007016:Hypophysectomy; D007165:Immunosuppression Therapy; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D023421:Models, Animal; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D011108:Polymers; D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I