Department of Chemical Engineering, Marmara University, Aydınevler, Maltepe, 34854, Istanbul, Turkey.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, BezmialemVakif University, 34093 Istanbul, Turkey; Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul University-Cerrahpasa, Buyukcekmece Campus, 34500 Istanbul, Turkey.
Int J Biol Macromol. 2023 May 15;237:123955. doi: 10.1016/j.ijbiomac.2023.123955. Epub 2023 Mar 9.
Core-shell structured lipidic nanoparticles (LNPs) were developed using lecithin sodium acetate (Lec-OAc) ionic complex as a core unit and quaternized inulin (QIn) as the shell part. Inulin (In) was modified using glycidyl trimethyl ammonium chloride (GTMAC) as a positively charged shell part and used for coating the negatively surface charged Lec-OAc. The critical micelle concentration (CMC) of the core was determined as 1.047 × 10 M, which is expected to provide high stability in blood circulation as a drug-carrying compartment. The amounts of curcumin (Cur) and paclitaxel (Ptx) loaded to LNPs (CurPtx-LNPs), and quaternized inulin-coated LNPs (Cur-Ptx-QIn-LNPs) were optimized to obtain mono-dispersed particles with maximum payload. The total amount of 2.0 mg of the drug mixture (1 mg Cur and 1 mg Ptx) was the optimized quantity for QIn-LNPs and CurPtx-QIn-LNPs due to the favorable physicochemical properties determined by dynamic light scattering (DLS) studies. This inference was confirmed by differential scanning calorimeter (DSC), and Fourier-transform infrared (FT-IR). SEM and TEM images clearly revealed the spherical shapes of LNPs and QIn-LNPs, and QIn covered the LNPs completely. The cumulative release measurements of Cur and Ptx from CurPtx-QIn-LNPs, along with the kinetic studies, showed a significant decrease in the release period of drug molecules with the effect of the coating. At the same time, Korsmeyer-Peppas was the best diffusion-controlled release model. Coating of the LNPs with QIn increased the cell-internalization of NPs to the MDA-MB-231 breast cancer cell lines, resulting in a better toxicity profile than the empty LNPs.
核壳结构脂质纳米粒（LNPs）以卵磷脂乙酸钠（Lec-OAc）离子复合物作为核心单元，季铵化菊粉（QIn）作为壳部分开发。菊粉（In）使用缩水甘油三甲氯化铵（GTMAC）作为正电荷壳部分进行修饰，并用于涂覆带负电荷的 Lec-OAc。核心的临界胶束浓度（CMC）确定为 1.047×10-3 M，预计作为药物输送隔室在血液循环中提供高稳定性。将姜黄素（Cur）和紫杉醇（Ptx）负载到 LNPs（CurPtx-LNPs）和季铵化菊粉涂覆的 LNPs（Cur-Ptx-QIn-LNPs）的量进行了优化，以获得具有最大载药量的单分散颗粒。由于动态光散射（DLS）研究确定的有利物理化学性质，药物混合物（1 mg Cur 和 1 mg Ptx）的总量 2.0 mg 是 QIn-LNPs 和 CurPtx-QIn-LNPs 的最佳用量。差示扫描量热法（DSC）和傅里叶变换红外（FT-IR）证实了这一推断。SEM 和 TEM 图像清楚地显示了 LNPs 和 QIn-LNPs 的球形形状，并且 QIn 完全覆盖了 LNPs。Cur 和 Ptx 从 CurPtx-QIn-LNPs 的累积释放测量以及动力学研究表明，随着涂层的作用，药物分子的释放期显著减少。同时，Korsmeyer-Peppas 是最佳扩散控制释放模型。QIn 对 LNPs 的涂层增加了 NPs 向 MDA-MB-231 乳腺癌细胞系的细胞内化，导致毒性特征优于空 LNPs。
