磷酸钙纳米颗粒药物递送系统在骨组织工程研究与应用中的优势

Advantages of calcium phosphate nanoparticles for drug delivery in bone tissue engineering research and application

背景:局部给药在骨组织工程应用中具备多种优势,以磷酸钙纳米颗粒作为载体的药物递送系统因其独特的优势已被广泛研究。目的:综述磷酸钙纳米颗粒药物递送系统在骨组织工程领域的最新研究进展及应用,展望其未来发展方向。方法:在中国知网、万方数据知识服务平台、Web of Science、PubMed数据库中进行相关文献检索,中、英文检索关键词为“磷酸钙颗粒,骨,药物递送,载药;calcium phosphate particle,calcium phosphate granule,bone,drug delivery”,通过纳入、排除标准筛选后,最终纳入60篇文献进行综述。结果与结论:羟基磷灰石、β-磷酸三钙、无定形磷酸钙及双相磷酸钙为最常用于药物递送的磷酸钙纳米颗粒,它们具有以下特性:良好的生物相容性和生物降解性;可控的粒径;高比表面积;温和的制备条件;pH值响应性。多数药物通过电荷与氢键作用吸附于磷酸钙纳米颗粒上,部分药物可与钙离子形成作用力较强的离子键或螯合物。磷酸钙纳米颗粒负载抗生素、双膦酸盐、生长因子、抗炎因子及核酸分子后展现出了有效保护、缓释药物及介导其入胞的作用,在体内外研究中均取得良好的促成骨效果。

BACKGROUND: Local drug delivery system has several advantages, and as an excellent carrier, calcium phosphate nanoparticles have been widely researched and applied in bone tissue engineering. OBJECTIVE: To review the development and applications of calcium phosphate nanoparticles for drug delivery in bone tissue engineering field, looking forward to its future development direction. METHODS: The literature search was performed in CNKI, Wanfang, Web of Science, and PubMed databases. The keywords were "calcium phosphate particles, bone, drug delivery, drug loading" in Chinese and "calcium phosphate particle, calcium phosphate granule, bone, drug delivery" in English. According to the inclusion and exclusion criteria, 60 articles were finally reviewed. RESULTS AND CONCLUSION: Hydroxyapatite, β-tricalcium phosphate, amorphous calcium phosphate and biphasic calcium phosphate were the most commonly used calcium phosphate nanoparticles for drug delivery. They showed some special properties: excellent biocompatibility and biodegradability, controlled particle size, high specific surface area, mild preparation conditions and pH responsiveness. Most drugs were adsorbed on calcium phosphate nanoparticles by charge and hydrogen bonding. Some drugs can form strong ionic bond or chelate with calcium ion. Loaded with growth factors, bisphosphonates, antibiotics, anti-inflammatory molecules and nucleic acids, calcium phosphate nanoparticles have shown effective protection, release drugs under control, and mediated their entry into cells, which have achieved good osteogenic effects both in vitro and in vivo.