title: Effect of particle size on zinc release from zinc containing tricalcium phosphate (ZnTCP) in Zn-deficient osteoporosis rats.
abstract: The effect of particle size on in vivo and in vitro Zn release of ZnTCP was investigated for the purpose of understanding Zn release behavior from a sustained-release device. The tricalcium phosphate powders (Ca2.7 Zn0.3(PO4)2), with particle size of 7.5 and 553 microm (S-ZnTCP and L-ZnTCP), including a 10 mol% of Zn (6.17 w/w%), as new sustained-release preparations, were synthesized by heating, after then ground and sieved using 38 and 300 microm screens. The different powder samples were characterized by the X-ray powder diffractometry and scanning electron microscopy. The release rates from Zn-TCP powders (10 mg) were measured in 10 ml of simulated body fluid (SBF) containing 10 mg/100 ml Ca2+(SBF/H), SBF containing 5 mg/100 ml Ca2+ (SBF/L) or SBF without Ca2+ (SBF/-) at 37.0 degrees C. The in vitro Zn release profiles for the smallest and the largest particles size of ZnTCP powders (L-ZnTCP and S-ZnTCP) at various Ca concentrations in SBF were significantly higher in SBF/- and SBF/L than in SBF/H. The Zn release rate from ZnTCP with different particle sizes were found to be inversely proportional to the concentration of calcium in SBF. After injection of a ZnTCP suspension containing 30 mg of S-ZnTCP powder on the backs of the rats, the plasma Zn level increased rapidly, reaching a concentration range of around 2 microg/ml. The area under the curve values of the plasma Zn concentration (Zn-AUC) over 6 days post injection of S-ZnTCP and L-ZnTCP were significantly higher than that of the control experiment. After the injection of S-ZnTCP and L-ZnTCP suspension, the plasma alkaline phosphatase activity (AIP) levels increased to more than 300 IU/l. In contrast, the AIP for the control decreased after 2 days. The area under the curve of the AIP (AIP-AUC) for 6 days of S-ZnTCP was significantly higher than that of other groups.
authors.affiliation: Kobe Pharmaceutical University, Motoyama-Kitamachi, Higashi-Nada, Kobe 658-8558, Japan. m-otsuka@kobepharma-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
authors.forename: Sunao
authors.initials: S
authors.lastname: Marunaka
authors.forename: Yoshihia
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naito
authors.forename: Noboru
authors.initials: N
authors.lastname: Ichinose
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kokubo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: William I
authors.initials: WI
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D002130:Calcium Phosphates / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D005260:Female; D008657:Metabolic Clearance Rate; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; C485817:beta-tricalcium phosphate; D015032:Zinc; C018392:tricalcium phosphate; D002118:Calcium