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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.


Related in: MedlinePlus

Photomicrographs of a bone defect in group B (slides stained with H&E stain, at 4 × magnification (A) and 10 × magnification (B)).Abbreviations: H&E, hematoxylin and eosin; px, pixels.
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f6-dddt-9-3599: Photomicrographs of a bone defect in group B (slides stained with H&E stain, at 4 × magnification (A) and 10 × magnification (B)).Abbreviations: H&E, hematoxylin and eosin; px, pixels.

Mentions: Histological and histomorphometrical analysis showed significantly more bone formation in group C when compared to groups A and B (Table 2). In group A, rhBMP-2 injected with isotonic saline, plasma levels of BMP-2 measured by ELISAs rapidly increased during the first 6 hours to more than 20 μg/L and then decreased to less than 5 μg/L within 48 hours (Figure 3). This result is in accordance with the histological examination, which revealed that there were few bony spicules embedded in a fibrous tissue filling the defect (Figure 4). Histomorphometrically, the repaired defects in group A were on average 19% ossified (Table 2). In group B (negative control), plasma levels of rhBMP-2 were untraceable during the entire 96-hour period of release (Figure 5). This is in accordance with the histological examination (Figure 6A and B), which revealed very few bone spicules in some slides and complete absence of any newly formed bone in others (Table 2), with mostly fibrous tissue filling the whole created defects. In group C (rhBMP-2 in NPs), the plasma level of rhBMP-2 slowly increased to 16 μg/L within 48 hours. After 48 hours, the plasma level did not decrease significantly but remained at a relatively steady plateau during the 4-day test period (Figure 7). This is in accordance with the histological examination, which showed extensive active bone formation surrounding the NPs, which were not yet completely resorbed. In general, the newly formed bone was mature with many distinct osteocytes. Multiple osteoblasts and blood vessels were seen all over the defects (Figure 8A–C). The newly formed bone volume was 78%.


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)

Photomicrographs of a bone defect in group B (slides stained with H&E stain, at 4 × magnification (A) and 10 × magnification (B)).Abbreviations: H&E, hematoxylin and eosin; px, pixels.
© Copyright Policy
Related In: Results  -  Collection

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

f6-dddt-9-3599: Photomicrographs of a bone defect in group B (slides stained with H&E stain, at 4 × magnification (A) and 10 × magnification (B)).Abbreviations: H&E, hematoxylin and eosin; px, pixels.
Mentions: Histological and histomorphometrical analysis showed significantly more bone formation in group C when compared to groups A and B (Table 2). In group A, rhBMP-2 injected with isotonic saline, plasma levels of BMP-2 measured by ELISAs rapidly increased during the first 6 hours to more than 20 μg/L and then decreased to less than 5 μg/L within 48 hours (Figure 3). This result is in accordance with the histological examination, which revealed that there were few bony spicules embedded in a fibrous tissue filling the defect (Figure 4). Histomorphometrically, the repaired defects in group A were on average 19% ossified (Table 2). In group B (negative control), plasma levels of rhBMP-2 were untraceable during the entire 96-hour period of release (Figure 5). This is in accordance with the histological examination (Figure 6A and B), which revealed very few bone spicules in some slides and complete absence of any newly formed bone in others (Table 2), with mostly fibrous tissue filling the whole created defects. In group C (rhBMP-2 in NPs), the plasma level of rhBMP-2 slowly increased to 16 μg/L within 48 hours. After 48 hours, the plasma level did not decrease significantly but remained at a relatively steady plateau during the 4-day test period (Figure 7). This is in accordance with the histological examination, which showed extensive active bone formation surrounding the NPs, which were not yet completely resorbed. In general, the newly formed bone was mature with many distinct osteocytes. Multiple osteoblasts and blood vessels were seen all over the defects (Figure 8A–C). The newly formed bone volume was 78%.

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.


Related in: MedlinePlus