Yousfan Amal, Moursel Nour, Hanano Abdulsamie
Department of Pharmaceutics and Pharmaceutical Technology, Pharmacy College, Al Andalus University for Medical Sciences, Tartus, Syria.
Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria (AECS), P.O. Box 6091, Damascus, Syria.
Sci Rep. 2024 Dec 30;14(1):32057. doi: 10.1038/s41598-024-83715-7.
Paclitaxel, a powerful anticancer drug, is limited by its poor water solubility and systemic toxicity, which hinder its effectiveness against aggressive brain tumors. This study aims to overcome these challenges by exploring novel intranasal delivery methods using lipid droplets (LDs) derived from date palm seeds (DPLDs) and mouse liver (MLLDs). The anticancer efficacy of PTX was evaluated using a comparative intranasal delivery approach. The lipid droplets were fractionated, and their physicochemical and biochemical properties were assessed. Our results showed that both DPLDs and MLLDs were spherical, with average diameters of 257 ± 36 nm and 416 ± 83 nm, respectively, and contained oil-rich cores of 392.5 and 612.4 mg mL. The MLLDs displayed a distinct lipid profile with low triglyceride content and high monoglyceride and diglyceride content. Conversely, the DPLDs primarily consisted of triglycerides, with stable granularity at around 83% and 79% for MLLDs and DPLDs, respectively. Both lipid droplets showed high encapsulation efficiencies, reaching 48.6 ± 3.2% and 45.4 ± 2.4% for MLLDs and DPLDs, respectively, after 4 h of incubation. The bio-distribution kinetics of paclitaxel post-intranasal administration demonstrated lower plasma paclitaxel levels in formulations compared to free paclitaxel. Notably, the accumulation of paclitaxel in the brain was significantly higher for paclitaxel-DPLD at early time points, with 1.527 ± 0.1% ID g and 2.4 ± 0.16% ID g at 5 and 30 min, respectively, compared to paclitaxel-MLLD and free paclitaxel. In Conclusion, the study highlights the potential of intranasal DPLD and MLLD formulations for enhanced brain targeting in brain tumor therapy, offering improved paclitaxel delivery and overcoming solubility and toxicity challenges.
紫杉醇是一种强效抗癌药物，但其水溶性差和全身毒性限制了它对侵袭性脑肿瘤的疗效。本研究旨在通过探索使用源自椰枣种子的脂质体（DPLD）和小鼠肝脏的脂质体（MLLD）的新型鼻内给药方法来克服这些挑战。采用比较鼻内给药方法评估了紫杉醇的抗癌疗效。对脂质体进行了分级分离，并评估了它们的物理化学和生化特性。我们的结果表明，DPLD和MLLD均呈球形，平均直径分别为257±36nm和416±83nm，并且含有富含油的核心，含量分别为392.5和612.4mg/mL。MLLD呈现出独特的脂质谱，甘油三酯含量低，单甘油酯和甘油二酯含量高。相反，DPLD主要由甘油三酯组成，MLLD和DPLD的稳定粒度分别约为83%和79%。两种脂质体均显示出高包封效率，孵育4小时后，MLLD和DPLD的包封效率分别达到48.6±3.2%和45.4±2.4%。鼻内给药后紫杉醇的生物分布动力学表明，与游离紫杉醇相比，制剂中的血浆紫杉醇水平较低。值得注意的是，在早期时间点，紫杉醇-DPLD在脑中的积累明显高于紫杉醇-MLLD和游离紫杉醇，在5分钟和30分钟时分别为1.527±0.1%ID/g和2.4±0.16%ID/g。总之，该研究突出了鼻内DPLD和MLLD制剂在脑肿瘤治疗中增强脑靶向性的潜力，提供了改进的紫杉醇递送并克服了溶解性和毒性挑战。
