Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation

Ali Habiballah Hassan,1 Khaled Mohamed Hosny,2,3 Zuahir A Murshid,1 Adel Alhadlaq,4 Ahmed Alyamani,5 Ghada Naguib6 1Department of Orthodontics, Faculty of Dentistry, 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Departme...

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Main Authors: Hassan AH, Hosny KM, Murshid ZA, Alhadlaq A, Alyamani A, Naguib G
Format: Article
Language:English
Published: Dove Medical Press 2015-07-01
Series:Drug Design, Development and Therapy
Online Access:http://www.dovepress.com/depot-injectable-biodegradable-nanoparticles-loaded-with-recombinant-h-peer-reviewed-article-DDDT
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author Hassan AH
Hosny KM
Murshid ZA
Alhadlaq A
Alyamani A
Naguib G
author_facet Hassan AH
Hosny KM
Murshid ZA
Alhadlaq A
Alyamani A
Naguib G
author_sort Hassan AH
collection DOAJ
description Ali Habiballah Hassan,1 Khaled Mohamed Hosny,2,3 Zuahir A Murshid,1 Adel Alhadlaq,4 Ahmed Alyamani,5 Ghada Naguib6 1Department of Orthodontics, Faculty of Dentistry, 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, 5Department of Oral Surgery, 6Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia 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.Materials and 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.Conclusion: 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.Keywords: BMP-2, biodegradable polymers, nanoparticle, PLGA, PCL, alveolar defects
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spelling doaj.art-05e572f8b0dd4351ab24344f8b61f6612022-12-21T17:48:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-07-012015default3599360622582Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluationHassan AHHosny KMMurshid ZAAlhadlaq AAlyamani ANaguib GAli Habiballah Hassan,1 Khaled Mohamed Hosny,2,3 Zuahir A Murshid,1 Adel Alhadlaq,4 Ahmed Alyamani,5 Ghada Naguib6 1Department of Orthodontics, Faculty of Dentistry, 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, 5Department of Oral Surgery, 6Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia 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.Materials and 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.Conclusion: 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.Keywords: BMP-2, biodegradable polymers, nanoparticle, PLGA, PCL, alveolar defectshttp://www.dovepress.com/depot-injectable-biodegradable-nanoparticles-loaded-with-recombinant-h-peer-reviewed-article-DDDT
spellingShingle Hassan AH
Hosny KM
Murshid ZA
Alhadlaq A
Alyamani A
Naguib G
Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
Drug Design, Development and Therapy
title Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
title_full Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
title_fullStr Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
title_full_unstemmed Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
title_short Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation
title_sort depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein 2 preparation characterization and in vivo evaluation
url http://www.dovepress.com/depot-injectable-biodegradable-nanoparticles-loaded-with-recombinant-h-peer-reviewed-article-DDDT
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