Elsewedy Heba S, Shehata Tamer M, Almostafa Mervt M, Soliman Wafaa E
Al Bilad Bank Scholarly Chair for Food and Security in Saudi Arabia, The Deanship of Scientific Research, The Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Alhofuf 36362, Saudi Arabia.
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Alhofuf 36362, Saudi Arabia.
Nanomaterials (Basel). 2022 Jun 23;12(13):2160. doi: 10.3390/nano12132160.
Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.
目前，高脂血症是一个日益严重的健康问题，被认为是肥胖的一个危险因素。在大多数情况下，控制体重和改变生活方式并不足够，这种情况需要药物治疗。他汀类药物（主要是阿托伐他汀（ATO））长期以来被广泛用作治疗血脂升高的药物，尤其是坏胆固醇，从而控制肥胖的发生率。然而，任何制剂面临的障碍都是药物的低溶解度。ATO的低溶解度导致其吸收不良以及生物利用度差。这为当前的研究铺平了道路，该研究旨在利用纳米技术开发某些能够容纳疏水性药物（如ATO）的纳米脂质载体。使用橄榄油制备了含有ATO的纳米结构脂质载体（NLC）。橄榄油是一种具有确认的降血脂活性的天然植物油，有助于提高制剂的疗效。通过应用质量源于设计（QbD）方法，基于合适的尺寸和更高的包封率选择了一种NLC配方进行优化。对优化后的ATO-NLC进行了zeta电位、体外研究和动力学曲线的考察。此外，还进行了稳定性测试和体内降血脂行为研究。优化后的NLC制剂似乎显示出粒径为（254.23 nm），zeta电位为中性（-1.77 mV），包封效率为（69.56%）。该制剂的释放时间可延长至12小时，释放率更高（97.17%）。稳定性测试证实了用聚乙二醇-二硬脂酰磷脂酰乙醇胺（PEG-DSPE）修饰制剂表面在提供高度稳定的制剂方面的作用，该制剂在两种不同条件下可耐受三个月的储存。最终，优化后的ATO-NLC能够成功降低肥胖诱导且喂食高脂饮食的大鼠的总胆固醇水平。值得注意的是，用橄榄油制备的ATO-NLC，除了屏蔽其表面外，还将提供一种稳定的制剂，支持橄榄油和ATO之间的协同作用。
