[关键词]
[摘要]
目的 制备载姜黄素两亲性星状聚酯纳米粒(Cur-NPs),以解决其稳定性差、生物利用度低等问题。方法 通过开环聚合反应和酯化反应合成两亲性星状聚酯(DPE-PCL-mPEG)作为纳米粒的载体材料,傅立叶变换显微红外光谱(FT-IR)、1H-NMR和凝胶渗透色谱(GPC)表征确定其结构和相对分子质量。溶剂挥发法制备Cur-NPs,考察其粒径、ξ电位、载药量、包封率。对Cur-NPs进行稳定性、体外释放、材料安全性、体外抗肿瘤和细胞摄取能力考察。结果 成功合成DPE-PCL-mPEG,制备的Cur-NPs平均粒径为(86.00±2.01)nm,ξ电位为(-9.40±0.09)mV,包封率为(95.51±1.23)%,载药量为(5.52±0.54)%。Cur-NPs具有良好的稳定性和缓释能力。细胞毒性、细胞摄取和体外抗肿瘤实验表明,空白纳米粒(blank-NPs)具有良好的生物安全性;相对于姜黄素溶液,Cur-NPs对人胶质瘤U251细胞的生长抑制作用更明显,并且具有更强的入胞能力。结论 Cur-NPs理化性质理想,能有效提高药物体外生物活性,为姜黄素的临床应用提供了新的解决方案。
[Key word]
[Abstract]
Objective Curcumin loaded amphiphilic star-shaped polyester nanoparticles (Cur-NPs) were prepared to improve the bioavailability of curcumin. Methods Amphiphilic star-shaped polymers (DPE-PCL-mPEG) were synthesized by ring-opening polymerization and esterification and used as the polymer precursor of nanoscale drug carrier. The structures of polymers were characterized by FT-IR spectroscopy and 1H-NMR. The molecular weights of polymers were determined via GPC. Cur-NPs were prepared by solvent evaporation. The physicochemical properties such as particle size, zeta potential, drug loading, encapsulation efficiency, stability, in vitro drug release behavior and cytotoxicity, anti-proliferation efficacy and cellular uptake of Cur-NPs were studied. Results DPE-PCL-mPEG was successfully synthesized. The particle size, ξ potential, encapsulation efficiency and drug loading of Cur-NPs was (86.00 ±2.01) nm, ξ potential (−9.40 ±0.09) mV, (95.51 ±1.23)% and (5.52 ±0.54)%, respectively. In addition, the nanoparticles exhibited good stability and sustained release ability. In vitro cytotoxicity demonstrated that blank nanoparticles (blank-NPs) had favorable biosafety. Cur-NPs exhibited stronger anti-proliferation efficacy and better cellular uptake ability against U251 cell. Conclusion Cur-NPs with ideal physicochemical properties were successfully prepared. This novel nanocarrier system can effectively improve the bioavailability of curcumin and have potential applications in drug delivery.
[中图分类号]
R283.6
[基金项目]
国家自然科学基金项目(22078297);浙江省自然科学基金项目(LY19B060012);浙江省药学会医院药学专项科研基金项目(2017ZYY28);浙江省药学会医院药学专项科研基金项目(2016ZYY35);台州市科技计划项目(1901ky49)