隐形顺铂聚乳酸纳米微粒对口腔鳞癌原发灶的靶向性研究

目的　研究隐形顺铂聚乳酸纳米微粒(CDDP-PLA-PEG-NP)的物理特性及对口腔鳞癌原发灶的靶向性。方法　用乳化溶剂蒸发法制备CDDP-PLA-PEG-NP;建立地鼠口腔颊鳞癌模型,并随机将64只动物分为实验组和对照组,每组各32只。实验组和对照组分别静脉注射CDDP-PLA-PEG-NP(6·6 mg/kg)和CDDP(1 mg/kg),每组于给药后0·083、0·5、1、2、4、6、12、24 h各处死4只动物。用高效液相色谱仪测定两组各时间点血浆和癌组织中药物浓度,求出CDDP-PLA-PEG-NP对口腔鳞癌原发灶的靶向指数、选择性指数和口腔鳞癌原发灶对CDDP-PLA-PEG-NP的相对摄取率。结果　CDDP-PLA-PEG-NP的平均粒径为(143·2±1·8)nm,粒径分布范围为103·5 ~175·8 nm,载药量和包封率分别为(15·2±0·9)%、(89.0±0·8)%;在8个时间点的靶向指数和选择性指数均远大于1,口腔癌组织对CDDP-PLA-PEG-NP的摄取量是CDDP的10·36倍。结论　CDDP-PLA-PEG-NP在动物体内对口腔鳞癌原发灶具有良好的靶向性,是具有发展前途的口腔癌纳米靶向给药系统。

Experimental Study of Cisplatin Loaded Polylactic Acid-polyethylene Glycol Nano-particles for Targeting Oral Carcinoma

OBJECTIVE: To investigate the target deliver of Cisplatin to oral carcinoma tissues by intravenous injection of Cisplatin loaded polylactic acid- polyethylene glycol nanoparticles (CDDP-PLA-PEG-NP). METHODS: CDDP-PLA-PEG-NP was prepared by the emulsion-solvent evaporation method. The buccal cancer model was established in 64 golden hamsters, which were divided randomly into two groups for 32 animals in each group, CDDP-PLA-PEG-NP (6.6 mg/kg) and CDDP (1 mg/kg) were respectively injected into mice tail vein. At 0.083, 0.5, 1, 2, 4, 6, 12, 24 h after drug administration. 4 animals in each group were sacrificed and CDDP concentration in the plasma and tumor were determined by high performance liquid chromatography. Targeting ability was evaluated by targeting index (TI), selectivity index (SI) and relative extraction efficiency (re). RESULTS: The average diameter of CDDP-PLA-PEG-NP was (143.2 +/- 1.8) nm. The diameter distribution was from 103.5 nm to 175.8 nm. Drug loading and embedding ratio were (15.2 +/- 0.9) %, (89.0 +/- 0.8) % respectively. Values of TI and SI are more than 1 at 8 time points. The area under CDDP concentration-time curve of oral carcinoma tissues in CDDP-PLA-PEG-NP group was 10.36 times as many as that in CDDP group. CONCLUSION: CDDP-PLA-PEG-NP can specifically deliver CDDP to oral carcinoma tissues by vein injection. Stealth anticancer nano-particle system can be regarded as a valuable drug deliver system to treat oral carcinoma.