College of Pharmacy, University of Sargodha, Sargodha, Pakistan; Department of Pharmacy, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Department of Pharmacy, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan.
Int J Pharm. 2020 May 15;581:119275. doi: 10.1016/j.ijpharm.2020.119275. Epub 2020 Mar 27.
Lipid polymer hybrid nanoparticles (LPHNPs) have been merged as potential nanocarriers for treatment of cancer. In the present study, LPHNPs loaded with Sorafenib (SFN) were prepared with PLGA, Lecithin and DSPE-PEG 2000 by using the bulk nanoprecipitation and microfluidic (MF) co-flow nanoprecipitation techniques. Herein, a glass capillary microfluidic device was primed to optimize the LPHNPs and compared to the bulk nanoprecipitation method. The morphological analysis of prepared LPHNPs revealed the well-defined spherical nano-sized particles in bulk nanoprecipitation method. Whereas, core shell morphology was observed in the MF method. The formulation prepared by the MF method (MF1-MF3) indicated relatively higher % EE (95.0%, 93.8% and 88.7%) and controlled release of the SFN from the particles as compared to the LPHNPs obtained by the bulk nanoprecipitation method. However, the release of SFN from all LPHNP formulation followed Higuchi model (R = 0.9901-0.9389) with Fickian diffusion mechanism. Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and powder X-rays diffraction (pXRD) studies depicted the compatibility of SFN with all the structural components. In addition, the colloidal stability, in vitro cytotoxicity and cell growth inhibition studies of LPHNPs also demonstrated stability in biological media, biocompatibility and safety with enhanced anti-proliferative effects than the free SFN in breast cancer and prostate cancer cells. In conclusion, LPHNPs provided a prospective platform for the cancer chemotherapy and substantially improved the knowledge of fabrication and optimization of the hybrid nanoparticles.
脂质聚合物杂化纳米粒子（LPHNPs）已被合并为治疗癌症的潜在纳米载体。在本研究中，通过使用 bulk nanoprecipitation 和微流控（MF）共流纳米沉淀技术，用 PLGA、卵磷脂和 DSPE-PEG 2000 制备了负载索拉非尼（SFN）的 LPHNPs。在此，使用玻璃毛细管微流控装置对 LPHNPs 进行了优化，并与 bulk nanoprecipitation 方法进行了比较。制备的 LPHNPs 的形态分析表明，在 bulk nanoprecipitation 方法中得到了形态良好的球形纳米级颗粒。而在 MF 方法中观察到了核壳形态。与 bulk nanoprecipitation 方法相比，MF 方法制备的配方（MF1-MF3）显示出相对较高的 % EE（95.0%、93.8%和 88.7%）和 SFN 从粒子中的控释。然而，所有 LPHNP 制剂的 SFN 释放均遵循 Higuchi 模型（R = 0.9901-0.9389），具有菲克扩散机制。傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和粉末 X 射线衍射（pXRD）研究表明 SFN 与所有结构成分相容。此外，LPHNPs 的胶体稳定性、体外细胞毒性和细胞生长抑制研究也表明，在生物介质中稳定、生物相容性和安全性，并且在乳腺癌和前列腺癌细胞中的增殖抑制作用优于游离 SFN。总之，LPHNPs 为癌症化疗提供了一个有前景的平台，并大大提高了对杂化纳米粒子的制造和优化的认识。
