Controlled release of porous calcium phosphate nanoparticles loaded with vitamin C

doi:10.3969/j.issn.2095-4344.2017.02.020

Abstract

Abstract:

BACKGROUND: It is reported that vitamin C can induce bone marrow mesenchymal stem cells differentiating into osteoblasts, and promote bone repair and regeneration. However, vitamin C solution is unstable, so a carrier is necessary.
OBJECTIVE: To observe the loading and controlled-release abilities of calcium phosphate used as the carrier of vitamin C.
METHODS: Calcium phosphate particles loaded with vitamin C were fabricated using chemical precipitation method, and the final concentration of vitamin C was 0, 0.1, 2 and 4 mmol/L, respectively. The drug-loaded capacity was detected. The release of vitamin from calcium phosphate nanoparticles in the simulate body fluid and ultrasonic environment was respectively evaluated. MC3T3-E1 cells were co-cultured with calcium phosphate nanoparticles loaded with 2 mmol/L vitamin C, or calcium phosphate nanoparticles only. The cell proliferation was detected at 1, 3, 5 and 7 days of culture, and the alkaline phasphatase activity was detected at 1, 5, 10 and 15 days of culture.
RESULTS AND CONCLUSION: The drug-loaded contents of calcium phosphate nanoparticles loading 0, 0.1, 2 and 4 mmol/L vitamin C were (59.9±5.4)%, (87.2±1.2)% and (28.4±26.3)%, respectively. Under normal environment, all samples could release vitamin C persistently, but the initial release speed of the particles carrying 0.1 and 2 mmol/L vitamin C was lower than that of particles carrying 4 mmd/L vitamin. Under ultrasonic environment, 2 mmol/L vitamin C-loaded calcium phosphate particles exhibited a quick release speed firstly that reached 5-15%, followed by a slow release speed. When ultrasonic powers kept at 75, 105 and 150 W, the release duration of vitamin C was 220, 340 and 260 minutes, respectively. MC3T3-E1 cell proliferation did not change after co-cultured with 2 mmol/L vitamin C-loaded calcium phosphate particles but the alkaline phosphatase activity was improved. These results suggest that calcium phosphate particles can be used as the carrier of vitamin C.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Calcium phosphates, Drug carriers, Asorbic Acid, Tissue Engineering

CLC Number:

R318

Kong Jun, Zhu Yong-qiang.

Controlled release of porous calcium phosphate nanoparticles loaded with vitamin C

[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(2): 273-279.

Figures/Tables 6

2.3 比表面积和孔径分布检测结果样品的比表面对药物负载和释放都有一定的影响，对样品的比表面积和孔径分布进行了测试，结果发现：0.1VC-CPSs和CPSs颗粒具有较发达的中孔(2-50 nm)和大孔，比表面积为 83.35 m2/g；2VC-CPSs颗粒的孔尺寸约为11 nm，具有大量的微孔，所以该样品比表面积较大，为95.87 m2/g；4VC-CPSs颗粒的比表面积最小，为77.64 m2/g，这可能是由于4VC-CPSs颗粒尺寸较大，而却只有少量微孔和较多大孔所导致；CPSs颗粒具有较多平均尺寸约为13 nm的微孔，比表面积为89.82 m2/g。通常情况下，载体的比表面越大负载的药物量越多。 2.4 载药量检测结果利用差重法检测了3种颗粒上所负载的维生素C量，其中2VC-CPSs样品具有较高的载药量，负载率高达(87.2±1.2)%；0.1VC-CPSs样品的维生素C负载率小于2VC-CPSs，为(59.9±5.4)%；4VC-CPSs样品负载率最低，为(28.4±26.3)%。药物负载率不仅与颗粒对维生素C的吸附量有关，还与颗粒表面和内部的孔结构有较大的关系。2VC-CPSs具有较发达的微孔，比表面积大，这种结构适合于包载和吸附维生素C。而0.1VC-CPSs样品具有较多中孔和大孔，比表面积小，表面吸附的药量也较少。4VC-CPSs样品表面大孔明显，比表面积最小，载药率不足。因此3种样品中，2VC-CPSs样品具有最高的载药量。 2.5 磷酸钙对维生素C控释的能力结果如图3所示，0.1VC-CPSs和2VC-CPSs的前期释放速率较慢， 4VC-CPSs前期释放速率较快，3种样品都有持续释药的特点。药物释放前12 d内，0.1VC-CPSs样品的释药速率为2.597 μg/d，随后的27 d内，速率增加到8.82 μg/d，之后释药速率急剧减少至0.44 μg/d；而2VC-CPSs样品前12 d的释药速率为74.4 μg/d，随后的45 d内药物较稳定地从载体中释放出来，其释药速率为147 μg/d，近2个月后速率减小为60.57 μg/d；4VC-CPSs样品释药前期没有出现较慢释放的现象，而是以约127.9 μg/d的释药速率持续释放了33 d，随后速率降为21 μg/d。所得到的磷酸钙颗粒对维生素C具有持久的控释能力，可能是由于维生素C与磷酸钙的羟基之间生成了氢键。但3种颗粒的药物释放率较低，均在55%以下，这可能是由于释药过程在常温常压环境中进行，对负载的维生素C的稳定性产生了影响，部分维生素C被氧化失效所导致。 "

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