Katiyar Sameer S, Ghadi Rohan, Kushwah Varun, Dora Chander Parkash, Jain Sanyog
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab 160062, India.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6760-6769. doi: 10.1021/acsbiomaterials.0c01290. Epub 2020 Dec 2.
The current investigation illustrates high drug loading of Paclitaxel (PTX) in lipid- and biosurfactant-based core-shell-type nanocapsules for improving therapeutic potential and reducing toxicity of PTX. The nanocapsules were prepared using the antisolvent precipitation technique having a particle size of 253.8 ± 15.4 nm and drug loading of ∼19%. The microscopic evaluation revealed the spherical shape of the nanocapsules and corroborated with the particle size obtained from Zetasizer. It also revealed the drug core enveloped by the relatively lighter shadowed region, that is, the layer of lipids and the biosurfactant. The release study showed biphasic and sustained release pattern of PTX from core-shell-type nanocapsules. In case of nanocapsules, the cellular uptake in the MCF-7 cell line was augmented ∼3.17-fold as compared to free PTX. Further, it was evident from the cytotoxicity assay that nanocapsules displayed greater cytotoxicity in MCF-7 cells and ∼2.98-fold decrease in the IC value as compared to free PTX. The apoptotic index observed in case of nanocapsules was ∼2.04-fold higher than that of free PTX. Furthermore, the pharmacokinetic profile of nanocapsules revealed a ∼7.21-fold increase in t and a ∼3.27-fold higher AUC compared to Intaxel. Finally, treatment with PTX core-shell-type nanocapsules demonstrated significant cutback in the % tumor burden and serum toxicity markers compared to marketed formulation. Thus, the current approach of core-shell-type nanocapsules with high drug loading can improve the current standards of PTX therapy for treatment of cancer.
当前的研究表明，在基于脂质和生物表面活性剂的核壳型纳米胶囊中，紫杉醇（PTX）具有较高的载药量，可提高其治疗潜力并降低PTX的毒性。采用反溶剂沉淀技术制备了纳米胶囊，其粒径为253.8±15.4nm，载药量约为19%。显微镜评估显示纳米胶囊呈球形，与Zetasizer测得的粒径相符。它还显示药物核心被相对较浅阴影区域包裹，即脂质层和生物表面活性剂层。释放研究表明，PTX从核壳型纳米胶囊中呈现双相和持续释放模式。对于纳米胶囊，MCF-7细胞系中的细胞摄取量与游离PTX相比增加了约3.17倍。此外，细胞毒性试验表明，纳米胶囊在MCF-7细胞中表现出更大的细胞毒性，与游离PTX相比，IC值降低了约2.98倍。纳米胶囊的凋亡指数比游离PTX高约2.04倍。此外，纳米胶囊的药代动力学曲线显示，与注射用紫杉醇相比，t增加了约7.21倍，AUC高约3.27倍。最后，与市售制剂相比，用PTX核壳型纳米胶囊治疗显示肿瘤负担百分比和血清毒性标志物显著降低。因此，当前这种高载药量核壳型纳米胶囊的方法可以提高PTX治疗癌症的现有标准。
