Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models
Abstract
:1. Introduction
2. Results and Discussion
2.1. Identification of dAsp3-PEG-PLGA and PEG-PLGA
2.2. Evaluation of GNCs and GNC Coupling with PLGA
2.3. Characterization of the Fluorescent NPs
2.4. Characterization of the SIM-Loaded APP NPs and PP NPs
2.5. Evaluation of the Cellular Uptake Pathway
2.6. Effects of the Formation of Mineralized Nodules
2.7. In Vivo Distribution Assay in Rats
2.8. In Vivo Experiments with OPs Models in Rats
3. Materials and Methods
3.1. Materials
3.2. Synthesis of dAsp3-PEG-PLGA and PEG-PLGA
3.3. Preparation of GNCs, Florescence NPs, and SIM NPs
3.4. Cell Culture and Related Evaluations
3.4.1. Cellular Uptake Pathway Study
3.4.2. In Vitro Analysis of SIM NPs on the Formation of Mineralized Nodules
3.5. In Vivo Distribution Assay and OP Treatment Models in Rats
3.5.1. In Vivo Distribution Assay of GNC-PLGA/APP NPs and GNC-PLGA/PP NPs in Rats
3.5.2. In Vivo Experiments with Rat OP Models
3.5.3. Postmenopausal OP
3.5.4. Disuse OP
3.6. Histological Analysis of Bone Tissue
3.7. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nanoparticles (NPs) | APP | GNC-PLGA/APP | PP | GNC-PLGA/PP |
---|---|---|---|---|
Average size (nm) | 213.5 | 247.8 | 130.5 | 225.5 |
Polydispersity index (PDI) | 0.116 | 0.029 | 0.024 | 0.005 |
SIM Nanocarriers | Average Size (nm) | Polydispersity Index (PDI) | Zeta Potential (mV) | EE% | DL (μg/mg) |
---|---|---|---|---|---|
SIM/APP NPs | 196.8 | 0.474 | −35.5 ± 1.2 | 72.48% | 0.28 |
SIM/PP NPs | 103.8 | 0.121 | −25.2 ± 0.5 | 76.29% | 0.31 |
Animal Model | Treatment Strategy | Dose and Duration | Main Findings | Reference |
---|---|---|---|---|
Rat [OVX] | Simvastatin (PO) | 0.3 to 10 mg/kg per day for 60 days | Simvastatin had no role in new bone formation and resorption. | Yao et al., 2006 [57] |
Rat [OVX] | Simvastatin (PO) | 10 and 20 mg/kg per day for 42 days | Simvastatin increased bone volume, osteoblast number, BMP-2, collagen type I, and osteocalcin. | Ho et al., 2009 [58] |
Rat [OVX] | Simvastatin (per oral) + 17-b-estradiol (IP) | 5 or 10 mg/kg per day for 42 days | Simvastatin improved lumbar vertebral bone mineral density and mechanical properties. Simvastatin exerted opposing modulatory effects on estrogen receptor-alpha (Erα) expression on bone and uterus in ovariectomized rats. | Li et al., 2011 [59] |
Rat [OVX] | SIM-loaded TC-PLGA NPs (IV) | 0.5 mg/kg/2 days for 60 days | The SIM-loaded TC-PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. | Wang et al., 2015 [29] |
Rat [OVX] | SIM/ASP6-LNPs (IV) | 1 mg/kg per 2 days for 60 days | SIM/ASP6-LNP nanocarriers can significantly improve the efficacy of SIM in the recovery of bone mineral density when compared with either SIM/LNPs or SIM alone. | Tao et al., 2020 [30] |
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Lin, C.-W.; Lee, C.-Y.; Lin, S.-Y.; Kang, L.; Fu, Y.-C.; Chen, C.-H.; Wang, C.-K. Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models. Int. J. Mol. Sci. 2022, 23, 10530. https://doi.org/10.3390/ijms231810530
Lin C-W, Lee C-Y, Lin S-Y, Kang L, Fu Y-C, Chen C-H, Wang C-K. Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models. International Journal of Molecular Sciences. 2022; 23(18):10530. https://doi.org/10.3390/ijms231810530
Chicago/Turabian StyleLin, Che-Wei, Chih-Yun Lee, Sung-Yen Lin, Lin Kang, Yin-Chih Fu, Chung-Hwan Chen, and Chih-Kuang Wang. 2022. "Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models" International Journal of Molecular Sciences 23, no. 18: 10530. https://doi.org/10.3390/ijms231810530