title: Controlled release of clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects.
abstract: This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n = 21, n = 7/time point). The defects were randomly designated to four groups. Group 1: No augmentation (sham), Group 2: beta-tricalcium phosphate (β-TCP), Group 3: β-TCP with 0.12 µg clarithromycin, and Group 4: β-TCP with 6.12 µg PLGA microspheres loaded with 0.12 µg Clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (µCT) and histology. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with ∼50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1. The µCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 201-208, 2018.
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Ali
authors.initials: A
authors.lastname: Alenezi
authors.affiliation: Oral Implant Center, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Terukina
authors.affiliation: Department of Oral and Maxillofacial Prosthodontics and Oral Implantology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Widyasri
authors.initials: W
authors.lastname: Prananingrum
authors.affiliation: Department of Oral and Maxillofacial Surgery and Oral Medicine, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Jinno
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tagami
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0001-7488-3588
authors.initials: S
authors.lastname: Galli
authors.affiliation: Department of Oral and Maxillofacial Surgery and Oral Medicine, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Ryo
authors.identifier: http://orcid.org/0000-0003-1945-1074
authors.initials: R
authors.lastname: Jimbo
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D017291:Clarithromycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012886:Skull / Q000293:injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017291:Clarithromycin
keywords: clarithromycin; drug delivery system; microspheres; sustained release