Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga (E), Mumbai 400 019, Maharashtra, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga (E), Mumbai 400 019, Maharashtra, India.
Int J Pharm. 2020 Mar 15;577:119082. doi: 10.1016/j.ijpharm.2020.119082. Epub 2020 Jan 24.
The aim of this study is to formulate thermodynamically stable docetaxel loaded nanostructured lipid carriers (DTX-NLCs) for parenteral cancer therapy with improved long term stability and better pharmacokinetic performance. DTX-NLCs were formulated using microemulsion (ME) template technique and characterized for particle size, entrapment efficiency (EE), drug content, and in vitro release kinetics. Further evaluation of NLCs was carried out by IR, DSC, and SEM analysis. The optimized formulation was subjected to stability studies as per ICH guidelines. In vivo pharmacokinetic studies were carried out using SD rats in comparison with a marketed formulation (MF). The particle size of optimized formulation was found to be in the range of 150-180 nm with EE of 68-70% and the SEM images illustrated spherical morphology. In vitro release of the formulation showed a sustained release of the drug from formulation compared to MF. The formulation was found to be stable for a period of 6 months at conditions of 30 °C/ 65%RH, 40 °C/ 75%RH, and 2-8 °C. In vitro cytotoxicity studies revealed better cytotoxic activity of DTX-NLCs than MF against various types of cancer cell lines. In vivo pharmacokinetic studies showed better performance with respect to half-life, volume of distribution, etc. (*p < 0.05, by unpaired t-test) of DTX-NLCs compared to MF.
本研究旨在制备热力学稳定的多西紫杉醇负载的纳米结构脂质载体（DTX-NLC），用于癌症的静脉给药治疗，以提高长期稳定性和更好的药代动力学性能。采用微乳液（ME）模板技术制备 DTX-NLC，并对其粒径、包封效率（EE）、药物含量和体外释放动力学进行了表征。通过 IR、DSC 和 SEM 分析对 NLC 进行了进一步评价。根据 ICH 指南对优化的配方进行了稳定性研究。通过与市售制剂（MF）进行比较，在 SD 大鼠中进行了体内药代动力学研究。优化配方的粒径在 150-180nm 之间，EE 为 68-70%，SEM 图像显示为球形形态。与 MF 相比，制剂的体外释放显示出药物的持续释放。该制剂在 30°C/65%RH、40°C/75%RH 和 2-8°C 条件下稳定期为 6 个月。体外细胞毒性研究表明，与 MF 相比，DTX-NLC 对各种类型的癌细胞系具有更好的细胞毒性。与 MF 相比，体内药代动力学研究表明 DTX-NLC 在半衰期、分布容积等方面具有更好的性能（*p<0.05，采用非配对 t 检验）。
