Al-Nemrawi Nusaiba K, Altawabeyeh Rowaida M, Darweesh Ruba S
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
J Pharm Sci. 2022 Feb;111(2):485-494. doi: 10.1016/j.xphs.2021.10.034. Epub 2021 Oct 30.
The conjugation of chitosan (CS) and folic acid (FA) was prepared and used to coat PLGA nanoparticles (NPs) that are loaded with Docetaxel (DTX) to target cancer cells that have lower pH and overexpression of folate receptors in comparison to normal cells. Three formulations had been prepared to reach the highest loading capacity (LC%) and encapsulation efficiency (EE%) and to study the effect of the amount of FA-CS on the drug release. The sizes, charges, homogeneity, surface morphology, LC% and EE% of the NPs were determined. The NPs were characterized using FTIR and XRD. In vitro release profiles of DTX from PLGA NPs, at pH 5.5 and 7.4 were determined. Finally, in vitro cytotoxicity assay on three cancer cell lines (RPMI 2650, Calu-3, and A549) was studied. The sizes of the three formulations ranged between 250.3±1.7 and 356.3±17.7. All prepared formulations showed acceptable monodispersity with highly positive charges. The EE% was above 85% and the LC% ranged between 6-35%. The in vitro release of DTX show an inverse relation to the amounts of FA-CS used and the pH of the dissolution medium. Coated PLGA NPs showed a significant difference in RPMI 2650, Calu-3, and A549 cell viability in comparison to free DTX. The NPs components were safe and non-toxic to human cells. In conclusion, coating PLGA NPs with FA-CS may be used as a good carrier for chemotherapeutic agents that selectively target carcinogenic tissues.
制备了壳聚糖（CS）与叶酸（FA）的共轭物，并用于包被负载多西他赛（DTX）的聚乳酸-羟基乙酸共聚物纳米粒（NPs），以靶向与正常细胞相比pH值较低且叶酸受体过表达的癌细胞。制备了三种制剂，以达到最高的载药量（LC%）和包封率（EE%），并研究FA-CS用量对药物释放的影响。测定了纳米粒的尺寸、电荷、均匀性、表面形态、LC%和EE%。使用傅里叶变换红外光谱（FTIR）和X射线衍射（XRD）对纳米粒进行了表征。测定了DTX在pH 5.5和7.4条件下从聚乳酸-羟基乙酸共聚物纳米粒中的体外释放曲线。最后，研究了对三种癌细胞系（RPMI 2650、Calu-3和A549）的体外细胞毒性试验。三种制剂的尺寸在250.3±1.7至356.3±17.7之间。所有制备的制剂均显示出可接受的单分散性，且带有高度正电荷。EE%高于85%，LC%在6%-35%之间。DTX的体外释放与所用FA-CS的量和溶解介质的pH呈反比关系。与游离DTX相比，包被的聚乳酸-羟基乙酸共聚物纳米粒在RPMI 2650、Calu-3和A549细胞活力方面显示出显著差异。纳米粒成分对人类细胞安全无毒。总之，用FA-CS包被聚乳酸-羟基乙酸共聚物纳米粒可作为一种良好的载体，用于选择性靶向致癌组织的化疗药物。
