In vitro and in vivo protein release and anti-ischemia/&lt;br /&gt;reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Fang, Shan; Liu, Yujuan; Jiang, Haiying; Tong, Fei

doi:10.2147/ijn.s146546

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…There are about a hundred published release studies with BMP-2 every year. In many cases, the release studies are carried out in PBS without any solubility increasing additives [9][10][11][12][13][14][15][16]. However, there are only a few publications that refer to the low solubility of the protein and the associated potential influence, both on the release itself (violation of sink conditions), and on the quantification of the partially aggregated protein [17].…”

Section: Introductionmentioning

confidence: 99%

Bone Morphogenetic Protein 2 (BMP-2) Aggregates Can be Solubilized by Albumin—Investigation of BMP-2 Aggregation by Light Scattering and Electrophoresis

et al. 2020

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Bone morphogenetic protein 2 (BMP-2) has a high tendency to aggregate at physiological pH and physiological ionic strength, which can complicate the development of growth factor delivery systems. The aggregation behavior in differently concentrated BMP-2 solutions was investigated using dynamic and static light scattering. It was found that at higher concentrations larger aggregates are formed, whose size decreases again with increasing dilution. A solubilizing effect and therefore less aggregation was observed upon the addition of albumin. Imaged capillary isoelectric focusing and the simulation of the surface charges of BMP-2 were used to find a possible explanation for the unusually low solubility of BMP-2 at physiological pH. In addition to hydrophobic interactions, attractive electrostatic interactions might be decisive in the aggregation of BMP-2 due to the particular distribution of surface charges. These results help to better understand the solubility behavior of BMP-2 and thus support future pharmaceutical research and the development of new strategies for the augmentation of bone healing.

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Section: Introductionmentioning

confidence: 99%

Bone Morphogenetic Protein 2 (BMP-2) Aggregates Can be Solubilized by Albumin—Investigation of BMP-2 Aggregation by Light Scattering and Electrophoresis

et al. 2020

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“…33 Furthermore, the micellar delivery system may provide more drug accumulated in bone tissues due to its nanosize effect. 34 Therefore, it represents a more effective and safe treatment compared to repeated local injections. Moreover, it was first reported that polymeric biomaterials combined with NOB and it made a suitable candidate for BTE.…”

Section: Introductionmentioning

confidence: 99%

<p>Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis</p>

Wang¹,

Xie²,

Ai³

et al. 2019

IJN

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Background: Nobiletin (NOB), a polymethoxy flavonoid, possesses anti-cancer and antiinflammatory activities, has been reported that it played role in anti-osteoporosis treatment. However, previous research did not focus on practical use due to lack of hydrophilicity and cytotoxicity at high concentrations. The aim of this study was to develop a therapeutic formulation for osteoporosis based on the utilization of NOB. Methods: In this study, NOB-loaded poly(ethylene glycol)-block-poly(e-caprolactone) (NOB-PEG-PCL) was prepared by dialysis method. The effects on osteoclasts and antiosteoporosis functions were investigated in a RANKL-induced cell model and ovariectomized (OVX) mice. Results: Dynamic light scattering and transmission electron microscopy examination results revealed that the NOB-PEG-PCL had a round shape, with a mean diameter around 124 nm. The encapsulation efficiency and drug loading were 76.34±3.25% and 7.60±0.48%, respectively. The in vitro release of NOB from NOB-PEG-PCL showed a remarkably sustained releasing characteristic and could be retained at least 48 hrs in pH 7.4 PBS. Anti-osteoclasts effects demonstrated that the NOB-PEG-PCL significantly inhibited the formation of tartrateresistant acid phosphatase (TRAP)-positive multinuclear cells stimulated by RANKL. Furthermore, the NOB-PEG-PCL did not produce cytotoxicity on bone marrow-derived macrophages (BMMs). The mRNA expressions of genetic markers of osteoclasts including TRAP and cathepsin K were significantly decreased in the presence of NOB-PEG-PCL. In addition, the NOB-PEG-PCL inhibited OC differentiation of BMMs through RANKL-induced MAPK signal pathway. After administration of the NOB-PEG-PCL, NOB-PEG-PCL prevented bone loss and improved bone density in OVX mice. These findings suggest that NOB-PEG-PCL might have great potential in the treatment of osteoporosis. Conclusion: The results suggested that NOB-PEG-PCL micelles could effectively prevent NOB fast release from micelles and extend circulation time. The NOB-PEG-PCL delivery system may be a promising way to prevent and treat osteoporosis.

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“…Even though BMP‐2 is already applied in clinical practice, not many studies have been done to determine their release profile in vivo . Most of the currently available data are dealing with in vitro studies .…”

Section: Introductionmentioning

confidence: 99%

The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate‐based implant‐coatings

Liu

Schouten

Boerman

et al. 2018

J Biomedical Materials Res

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Biomimetically deposited calcium phosphate-based coatings of prostheses can serve as a vehicle for the targeted delivery of growth factors to the local implant environment. Based on indirect evidence in previous studies we hypothesize that such agents are liberated gradually from the coating via a cell-mediated degradation. In the present study, we tested this hypothesis by investigating the release mechanism and its kinetics by use of a radiolabeled osteogenic agent ( I-BMP-2) under conditions in which native cell populations with a coating-degradative potential were either absent or present. The release of I-BMP-2 was monitored for 5 weeks, either in vitro or after implantation at an ectopic (subcutaneous) site in rats in vivo. Only from implants that bore a coating-incorporated depot of bone morphogenetic protein 2 (BMP-2) was the agent released slowly and steadily over 5 weeks, that is, 50% of the loaded dose was liberated in vivo (5 to 10% weekly), as against 14.6% in vitro (less than 1% weekly). The coatings bearing an incorporated depot of BMP-2 underwent significant cell-mediated degradation, whereas under cell-free conditions no degradation occurred, and the spontaneous release of BMP-2 was negligible. Our findings confirm this carrier system to be a suitable vehicle for the sustained and cell-mediated delivery of BMP-2. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2363-2371, 2018.

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In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Cited by 14 publications

References 51 publications

Bone Morphogenetic Protein 2 (BMP-2) Aggregates Can be Solubilized by Albumin—Investigation of BMP-2 Aggregation by Light Scattering and Electrophoresis

Bone Morphogenetic Protein 2 (BMP-2) Aggregates Can be Solubilized by Albumin—Investigation of BMP-2 Aggregation by Light Scattering and Electrophoresis

<p>Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis</p>

The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate‐based implant‐coatings

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