title: Preparation and in vivo evaluation of PCADK/PLGA microspheres for improving stability and efficacy of rhGH.
abstract: The goal of this research is to prepare poly(cyclohexane-1,4 diyl acetone dimethylene ketal) (PCADK)/poly(D,L-lactide-co-glycolide) (PLGA) blend microspheres loaded with recombinant human growth hormone (rhGH). The effect of PCADK degradation products on the structural integrity, secondary and tertiary structure and pharmacodynamics of rhGH was evaluated by native-polyacrylamide gel electrophoresis (Native-PAGE), size-exclusion high performance liquid chromatography (SEC-HPLC), circular dichroism (CD), fluorescence spectroscopy and in hypophysectomized rat models. Compared with PLGA degradation products, rhGH was found to be more stable in the presence of PCADK degradation products. PCADK/PLGA blend microspheres were then prepared and the morphology, encapsulation efficiency, release behavior and rhGH stability were investigated. PCADK/PLGA microspheres had regular shapes and smooth surfaces when the proportion of PCADK was less than 50%. The late-releasable amount of rhGH in PCADK/PLGA microspheres was greater than that in PLGA microspheres. In addition, the PCADK/PLGA microspheres showed larger AUC and improved therapeutic effects on rats than PLGA microspheres. Furthermore, the pH inside the microspheres was detected by CLSM to explain the improved rhGH stability in the PCADK/PLGA microspheres. In conclusion, PCADK/PLGA blend microspheres showed potential to improve rhGH stability and the efficacy of sustained-release of rhGH compared with PLGA microspheres.
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: sunfengying@jlu.edu.cn.
authors.forename: Fengying
authors.initials: F
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: liyouxin@jlu.edu.cn.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D065546:Drug Liberation; D004355:Drug Stability; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D011108:Polymers; D011994:Recombinant Proteins; C517410:poly(cyclohexane-1,4-diyl acetone dimethylene ketal); D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I
keywords: Compatibility; Efficacy; Microspheres; PCADK; Recombinant human growth hormone (rhGH); pH