title: Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation.
abstract: OBJECTIVE
  The aim of this study is to utilize the biocompatibility characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA) and polycaprolactone (PCL), to prepare sustained-release injectable nanoparticles (NPs) of bone morphogenetic protein-2 (BMP-2) for the repair of alveolar bone defects in rabbits. The influence of formulation parameters on the functional characteristics of the prepared NPs was studied to develop a new noninvasive injectable recombinant human BMP-2 (rhBMP-2) containing grafting material for the repair of alveolar bone clefts.
  
  
  METHODS
  BMP-2 NPs were prepared using a water-in-oil-in-water double-emulsion solvent evaporation/extraction method. The influence of molar ratio of PLGA to PCL on a suitable particle size, encapsulation efficiency, and sustained drug release was studied. Critical size alveolar defects were created in the maxilla of 24 New Zealand rabbits divided into three groups, one of them treated with 5 μg/kg of rhBMP-2 NP formulations.
  
  
  RESULTS
  The results found that NPs formula prepared using blend of PLGA and PCL in 4:2 (w/w) ratio showed the best sustained-release pattern with lower initial burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size, and more than 90% in vitro release. So, this formula was selected for scanning electron microscope examination and in vivo evaluation. Histomorphometric analysis showed 78% trabecular bone fill, mostly mature bone in the defects treated with rhBMP-2 in NPs within 6 weeks.
  
  
  CONCLUSIONS
  The prepared NPs prolonged the release and the residence time of rhBMP-2 in rabbits, which led to the formation of adequate bone in critical size alveolar bone defects in 6 weeks. This noninvasive method has application for the primary restoration of alveolar bone defects.
authors.affiliation: Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ali Habiballah
authors.initials: AH
authors.lastname: Hassan
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt.
authors.forename: Khaled Mohamed
authors.initials: KM
authors.lastname: Hosny
authors.affiliation: Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Zuahir A
authors.initials: ZA
authors.lastname: Murshid
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Adel
authors.initials: A
authors.lastname: Alhadlaq
authors.affiliation: Department of Oral Surgery, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Alyamani
authors.affiliation: Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ghada
authors.initials: G
authors.lastname: Naguib
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: BMP-2; PCL; PLGA; alveolar defects; biodegradable polymers; nanoparticle