Pharmaceutical Technology Department, National Research Centre, El-Buhouth Street, Dokki, Cairo 12622, Egypt.
Pharmacology Department, National Research Centre, El-Buhouth St., Dokki, Cairo 12622, Egypt.
Int J Pharm. 2023 Sep 25;644:123314. doi: 10.1016/j.ijpharm.2023.123314. Epub 2023 Aug 12.
The aim of the current study is to preserve the emulsomal vesicles against the harsh condition of gastrointestinal tract (GIT), after oral administration, employing tripolyphosphate (TPP)-crosslinked chitosan as a protective coating layer. Rutin was used as a model drug with evaluation of anti-hyperlipidemic activity in rats. The rutin loaded unmodified emulsomes were prepared using tripalmitin and soybean phosphatidylcholine (SPC), by thin film method. Drug loading for the prepared formulations ranged between 6.80 and 15.50 %. The selected formulation (RT-Emuls-6) comprised tripalmitin and SPC, molar ratio 1:1, and exhibited particle size (PS) and zeta potential (ZP) of 150.40 nm and -35.35 mV, respectively. RT-Emuls-6 was then modified by coating with either solely chitosan (RT-Emuls-6-Ch) or TPP-crosslinked chitosan (RT-Emuls-6-Ch-TPP-1). The latter exhibited PS and ZP values of 269.60 nm and 37.17 mV, respectively. Transmission electron microscopy of RT-Emuls-6-Ch-TPP-1 showed a dense pale greyish layer of a coating layer of chitosan crosslinked with TPP surrounding SPC bilayers. Fourier transform infrared spectroscopy analysis along with X-ray powder diffraction confirmed cross-linking between chitosan and TPP. Stability study in the simulated GIT fluids revealed that the order of rutin retained percentage was RT-Emuls-6-Ch-TPP-1 > RT-Emuls-6-Ch > RT-Emuls-6 (80.02, 50.66 and 44.41 %, respectively for simulated gastric fluid and 63.50, 55.66 and 24.00 %, respectively for simulated intestinal fluid, after 2 h incubation). Anti-hyperlipidemic activity of rutin loaded emulsomes was evaluated, after oral administration, in a high fat diet-induced hyperlipidemia in rats. The order of activity was as follows: RT-Emuls-6-Ch-TPP-1 > RT-Emuls-6-Ch > RT-Emuls-6 > free rutin. These findings revealed the potential of TPP-crosslinked chitosan as a protective coating layer for enhancing the stability of emulsomes against the harsh condition of GIT. RT-Emuls-6-Ch-TPP-1 had a potent anti-hyperlipidemic activity via regulation of lipids, oxidative stress, irisin and uncoupling protein 1.
本研究的目的是通过使用三聚磷酸交联壳聚糖作为保护性涂层，在口服后保护乳状液免受胃肠道（GIT）恶劣条件的影响。芦丁被用作模型药物，以评估其在大鼠中的抗高血脂活性。使用三棕榈酸甘油酯和大豆磷脂酰胆碱（SPC）通过薄膜法制备未修饰的芦丁负载乳状液。所制备制剂的药物载量在 6.80%至 15.50%之间。选择的配方（RT-Emuls-6）由三棕榈酸甘油酯和 SPC 组成，摩尔比为 1:1，粒径（PS）和 Zeta 电位（ZP）分别为 150.40nm 和-35.35mV。然后通过单独用壳聚糖（RT-Emuls-6-Ch）或三聚磷酸交联壳聚糖（RT-Emuls-6-Ch-TPP-1）进行涂层修饰 RT-Emuls-6。后者的 PS 和 ZP 值分别为 269.60nm 和 37.17mV。RT-Emuls-6-Ch-TPP-1 的透射电子显微镜显示出围绕 SPC 双层的壳聚糖与三聚磷酸交联的致密淡灰色涂层层。傅里叶变换红外光谱分析和 X 射线粉末衍射证实了壳聚糖和三聚磷酸之间的交联。在模拟胃肠道液中的稳定性研究表明，芦丁保留率的顺序为 RT-Emuls-6-Ch-TPP-1>RT-Emuls-6-Ch>RT-Emuls-6（分别为模拟胃液 2 小时孵育后 80.02%、50.66%和 44.41%，模拟肠液分别为 63.50%、55.66%和 24.00%）。在高脂肪饮食诱导的大鼠高血脂症中，口服芦丁负载乳状液的抗高血脂活性进行了评估。活性顺序如下：RT-Emuls-6-Ch-TPP-1>RT-Emuls-6-Ch>RT-Emuls-6>游离芦丁。这些发现表明，三聚磷酸交联壳聚糖作为保护性涂层具有增强乳状液对胃肠道恶劣条件的稳定性的潜力。RT-Emuls-6-Ch-TPP-1 通过调节脂质、氧化应激、鸢尾素和解偶联蛋白 1 具有很强的抗高血脂活性。
