Reddy L Harivardhan, Vivek K, Bakshi Nishant, Murthy R S R
Drug Delivery Research Laboratory, Center of Relevance and Excellence in NDDS, Pharmacy Department, M.S. University, Baroda, Gujarat, India.
Pharm Dev Technol. 2006;11(2):167-77. doi: 10.1080/10837450600561265.
Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 500C, compared to those stored at 30 degrees C and 4 degrees C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC-loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t(1/2) and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.
采用乳化和高压均质技术制备了固体脂质纳米粒（SLN），并通过粒径分析和差示扫描量热法对其进行了表征。研究了均质压力、时间和表面活性剂浓度等实验因素对纳米粒粒径和分布的影响，以优化制剂配方。结果发现，在15000 psi下均质3个循环效果最佳，可得到粒径更小的纳米粒。对于硬脂酸甘油酯SLN（TSSLN）、三棕榈酸甘油酯SLN（TPSLN）和山嵛酸甘油酯SLN（GBSLN），使用3%牛磺胆酸钠可得到相对较小粒径的纳米粒。将抗癌药物柠檬酸他莫昔芬（TC）负载到SLN中。与TPSLN（86.75%）和GBSLN（98.64%）相比，负载TC的TSSLN的包封率较低（78.78%）。短期稳定性研究表明，与在30℃和4℃储存的纳米粒相比，在50℃储存时纳米粒的粒径显著增大。在所研究的所有类型纳米粒中，储存时颗粒的不稳定程度依次为日光>人工光>黑暗。建立并验证了一种紫外（UV）分光光度法用于测定大鼠血浆中的他莫昔芬。将负载TC的TSSLN静脉注射给大鼠，并测定血浆中的药代动力学参数。负载TC的TSSLN在血浆中的t(1/2)和平均驻留时间分别比游离他莫昔芬高约3.5倍（p < 0.001）和3倍（p < 0.001），表明负载TC的TSSLN具有作为血液中长循环系统的潜力。因此，上述固体脂质纳米粒可通过增强的渗透滞留（EPR）效应成为将他莫昔芬递送至癌组织的有益系统。
