Controlled release of growth hormone from thermosensitive triblock copolymer systems: In vitro and in vivo evaluation.
The purpose of this study was to design injectable controlled release polymer formulations for growth hormone using triblock copolymer PLGA-PEG-PLGA (MW 1400-1000-1400). Porcine growth hormone (pGH) formulations were prepared by adding pGH into 30% (w/v) aqueous solution of triblock copolymer. pGH concentrations in the released samples were determined using a standard MicroBCA method. In vitro release studies demonstrated that there were no initial burst of pGH from both formulations containing a low dose (0.12%, w/v) and a high dose (0.42%, w/v) of pGH. In vivo absorption study of pGH in rabbits showed that constant serum levels of exogenous pGH (3-7 ng/mL from high dose and 2-4 ng/mL from low dose) were detected for nearly 4 weeks from delivery systems upon single subcutaneous injection. The absolute bioavailability of pGH enhanced from the thermosensitive polymer-based systems, which was approximately 5-15-fold those of subcutaneous aqueous solution. MTT assay and light microscopy were used to investigate the in vitro and in vivo biocompatibility of thermosensitive polymer delivery systems, respectively. Both in vitro and in vivo results support the biocompatible nature of these polymer delivery systems. Thus, the triblock copolymer used in this study was able to control the release of incorporated pGH in vitro and in vivo for longer duration and the delivery system was biocompatible.
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, ND 58105, USA.
Sibao
S
Chen
Jagdish
J
Singh
D000818:Animals; D041702:BALB 3T3 Cells; D001672:Biocompatible Materials; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D013006:Growth Hormone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011098:Polyglactin 910 / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D012995:Solubility; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D013006:Growth Hormone