The purpose of this paper was to investigate the possibility of developing a polymeric nanoparticle delivery system for ORI to increase its solubility, blood circulation time and tissue targeting. Oridonin-loaded poly (D, L-lactic acid) nanoparticles (ORI-PLA-NP) were prepared by the further modified spontaneous emulsion solvent diffusion (MSESD) method. Studies were carried out to characterize and evaluate the produced ORI-PLA-NP both in vitro and in vivo. The experimental results showed that the mean size of the nanoparticles were 137.3nm, with 87.2% of the nanoparticles distributed between the range of 107 and 195nm. The entrapment efficiency and actual drug loading of the nanoparticles were 91.88±1.83 and 2.32±0.05%, respectively. It was demonstrated by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) that ORI existed in the form of amorphous in the nanoparticles. The in vitro release profile of ORI-PLA-NP could be expressed well by the Higuchi equation: Q=8.944t1/2+11.246. The results of pharmacokinetics demonstrated that being encapsulated in PLA nanoparticles was remarkably effective for ORI to prolong its blood circulation time. After the i.v. administration of ORI-PLA-NP, we could observe a stable and high concentration of ORI in liver, lung and spleen, while its distribution in heart and kidney decreased.

The purpose of the present study was to investigate the effects of particle size on the pharmacokinetics and tissue distribution of oridonin nanosuspensions after intravenous administration. Two oridonin nanosuspensions with markedly different size were prepared by high pressure homogenization method. The particle size of nanosuspension A is 103.3±1.5nm, while B is 897.2±14.2nm. Dissolution studies showed that complete dissolution could be obtained within 10min for nanosuspension A, however, nanosuspension B showed a slower dissolution, only 85.2% dissolved by 2h. The pharmacokinetics and tissue distribution of oridonin nanosuspensions A and B were studied after intravenous administration using New Zealand rabbits and Kunming mice as experimental animals, respectively. An Oridonin control solution was studied parallelly. The results showed that oridonin nanosuspension A exhibited pharmacokinetic and biodistribution properties similar to solution due to its rapid dissolution in blood circulation. Oridonin nanosuspension B, however, showed a high uptake in RES organs, meanwhile exhibited a markedly different pharmacokinetic property compared to nanosuspension A. These differences could be attributed to the different particle size of the two nanosuspensions considering their zeta potential had no significant difference. In conclusion, particle size showed obvious effects on pharmacokinetics and tissue distribution of nanosuspensions.

目的以冬凌草甲素为模型药物，以硬脂酸为载体材料制备冬凌草甲素固态类脂纳米粒，并考察其质量和性质。方法用乳化蒸发一低温固化技术制得了冬凌草甲紊固态夹脂纳米粒，并对其形态、粒径、表面电位、包封率、结构和质量、体外释药特性等进行了研究。结果得到的硬脂酸固态类脂纳米粒为类球形实体，担轻分布比较均匀，平均粒径dav=（22.22±15.5）nm；电位-45.07mY；包封率为（44.83±1.504）%；药物体外释放符合Higuchi方程。用DSC和X-射线衍射分析证明纳米粒确已形成。结论冬凌草甲素可以制成硬脂酸纳米粒，各项物理指标稳定。

目的综述了近30年来国内外有关冬凌草甲素的研究进展。方法分析和归纳了有关冬凌草甲素的结构性质、含量测定方法、荆型研究、药理作用厦临床应用的文献报道。结果与讨论冬凌草甲素的研究主要集中在抗肿瘤活性及机制方面。提取分离和含量测定方法的研究也比较多，但对新剂型及药物动力学的研究较少。