Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, via del Liceo 1, 06123 Perugia, Italy.
Int J Pharm. 2013 Sep 15;454(1):316-23. doi: 10.1016/j.ijpharm.2013.06.037. Epub 2013 Jul 4.
The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery.
Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4°C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate(®) 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation.
Data showed nanoparticle stability at 4°C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4°C. Chorioallantoic membrane assay and rat brain histology showed the absence of acute toxicity corroborating previously published data.
Cetylpalmitate nanoparticle long-term physical and chemical stability, together with the in vivo safety, corroborate the existing evidences of the high value of colloidal lipids as parenteral formulations and carriers for brain drug delivery.
本研究旨在评估用于脑部药物递送的脂质纳米粒的长期稳定性和安全性。
采用高压均质法制备脂质纳米粒，在室温及 4°C 下储存，实时监测其平均水动力直径和高斯分布宽度。通过核磁共振技术对诊断信号进行检测，以评估十六烷酸鲸蜡酯和聚山梨酯（®）80 的化学完整性。通过鸡胚绒毛尿囊膜实验和啮齿动物脑组织学评估来评估纳米粒的毒性。
数据显示，脂质纳米粒在 4°C 下可稳定 4 年以上，粒径仅略有增加，而在室温下，9 个月后就会发生不稳定。核磁共振研究证实，在 4°C 下储存 4 年后，脂质基质和表面活性剂的化学降解率<5%。鸡胚绒毛尿囊膜实验和大鼠脑组织学研究表明，纳米粒无急性毒性，这与先前发表的数据相符。
十六烷酸鲸蜡酯纳米粒的长期物理和化学稳定性，以及体内安全性，证实了胶体脂质作为注射制剂和脑部药物递送载体的高价值。
