Han C, Qi C M, Zhao B K, Cao J, Xie S Y, Wang S L, Zhou W Z
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
J Vet Pharmacol Ther. 2009 Apr;32(2):116-23. doi: 10.1111/j.1365-2885.2008.01009.x.
Tilmicosin-loaded solid lipid nanoparticles (SLN) were prepared with hydrogenated castor oil (HCO) by o/w emulsion-solvent evaporation technique. The nanoparticle diameters, surface charges, drug loadings and encapsulation efficiencies of different formulations were 90 approximately 230 nm, -6.5 approximately -12.5 mV, 40.3 approximately 59.2% and 5.7 approximately 11.7% (w/w), respectively. In vitro release studies of the tilmicosin-loaded nanoparticles showed a sustained release and the released tilmicosin had the same antibacterial activity as that of the free drug. Pharmacokinetics study after subcutaneous administration to Balb/c mice demonstrated that a single dose of tilmicosin-loaded nanoparticles resulted in sustained serum drug levels (>0.1 microg/mL) for 8 days, as compared with only 5 h for the same amount of tilmicosin phosphate solution. The time to maximum concentration (Tmax), half-life of absorption (T(1/2) ab) and half-life of elimination (T(1/2) el) of tilmicosin-loaded nanoparticles were much longer than those of tilmicosin phosphate solution. Tissue section showed that drug-loaded nanoparticles caused no inflammation at the injection site. Cytotoxicity study in cell culture and acute toxicity test in mice demonstrated that the nanoparticles had little or no toxicity. The results of this exploratory study suggest that the HCO-SLN could be a useful system for the delivery of tilmicosin by subcutaneous administration.
采用油包水（o/w）乳液-溶剂蒸发技术，用氢化蓖麻油（HCO）制备了载替米考星的固体脂质纳米粒（SLN）。不同制剂的纳米粒直径、表面电荷、载药量和包封率分别约为90至230nm、-6.5至-12.5mV、40.3至59.2%和5.7至11.7%（w/w）。载替米考星纳米粒的体外释放研究显示为缓释，且释放出的替米考星具有与游离药物相同的抗菌活性。对Balb/c小鼠皮下给药后的药代动力学研究表明，单剂量的载替米考星纳米粒可使血清药物水平持续8天保持在>0.1μg/mL，而相同剂量的替米考星磷酸盐溶液仅能维持5小时。载替米考星纳米粒的达峰时间（Tmax）、吸收半衰期（T(1/2) ab）和消除半衰期（T(1/2) el）均远长于替米考星磷酸盐溶液。组织切片显示，载药纳米粒在注射部位未引起炎症。细胞培养中的细胞毒性研究和小鼠急性毒性试验表明，纳米粒几乎没有毒性。这项探索性研究的结果表明，HCO-SLN可能是一种通过皮下给药递送替米考星的有用体系。
