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

Hassan AH, Hosny KM, Murshid ZA, Alhadlaq A, Alyamani A, Naguib G - Drug Des Devel Ther (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

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.

No MeSH data available.


Release of rhBMP-2 from nanoparticles prepared with various PLGA:PCL ratios.Abbreviations: rhBMP-2, recombinant human bone morphogenetic protein-2; PLGA, poly lactide-co-glycolide; PCL, polycaprolactone.
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f2-dddt-9-3599: Release of rhBMP-2 from nanoparticles prepared with various PLGA:PCL ratios.Abbreviations: rhBMP-2, recombinant human bone morphogenetic protein-2; PLGA, poly lactide-co-glycolide; PCL, polycaprolactone.

Mentions: The cumulative percentages of rhBMP-2 released from NPs based on different PLGA:PCL ratios as a function of time are shown in Figure 2. The slowest release was obtained at a PLGA:PCL ratio of 4:4, but the cumulative percentage of BMP-2 released at the end of the test was 60% only. Formula F3 prepared by PLGA:PCL at ratio 4:2 released BMP-2 in controlled manner, and the release pattern kinetically followed Higuchi diffusion model and at same time showed high percentage of BMP-2 release, and hence, this formula was selected for in vivo study.


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

Hassan AH, Hosny KM, Murshid ZA, Alhadlaq A, Alyamani A, Naguib G - Drug Des Devel Ther (2015)

Release of rhBMP-2 from nanoparticles prepared with various PLGA:PCL ratios.Abbreviations: rhBMP-2, recombinant human bone morphogenetic protein-2; PLGA, poly lactide-co-glycolide; PCL, polycaprolactone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507488&req=5

f2-dddt-9-3599: Release of rhBMP-2 from nanoparticles prepared with various PLGA:PCL ratios.Abbreviations: rhBMP-2, recombinant human bone morphogenetic protein-2; PLGA, poly lactide-co-glycolide; PCL, polycaprolactone.
Mentions: The cumulative percentages of rhBMP-2 released from NPs based on different PLGA:PCL ratios as a function of time are shown in Figure 2. The slowest release was obtained at a PLGA:PCL ratio of 4:4, but the cumulative percentage of BMP-2 released at the end of the test was 60% only. Formula F3 prepared by PLGA:PCL at ratio 4:2 released BMP-2 in controlled manner, and the release pattern kinetically followed Higuchi diffusion model and at same time showed high percentage of BMP-2 release, and hence, this formula was selected for in vivo study.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

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.

No MeSH data available.