Zaheer Yumna, Ali Muhammad Asim, Rehman Mubashar, Iftikhar Maryam, Anwar Samina, Ali Asad, Mobeen Ameena, Iqbal Mazhar, Iqbal Samina, Younis Muhammad Rizwan, An Ruibing, Dong Jian, Ihsan Ayesha
National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan.
Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Colloids Surf B Biointerfaces. 2025 Mar;247:114423. doi: 10.1016/j.colsurfb.2024.114423. Epub 2024 Dec 4.
Naringenin (Nrg) is the most abundant natural dietary flavonoid with promising anti-inflammatory potential. However, its therapeutic application is limited due to poor absorption, low bioavailability, and inability to cross physiological barriers. Herein, we designed biocompatible solid lipid nanoparticles (SLNs) to overcome these challenges and to enhance the oral bioavailability and therapeutic potential of Nrg. Nrg-loaded solid lipid nanoparticles (Nrg-SLNs) were fabricated from natural fatty acids, stearic (Nrg-SANPs), or a combination of stearic and lauric acid as binary nanoparticles (Nrg-SLNPs) by the hot melt encapsulation technique. The optimized Nrg-loaded nanoparticles exhibited a hydrodynamic diameter of 74 nm for SANPs and 91 nm for SLNPs, a zeta potential of -25 mV to -37 mV, and entrapment efficiency ranging from 79 % to 85 %. Electron paramagnetic resonance (EPR) spectroscopy indicated an in vitro radical protection factor (RPF) of 215 ± 2 × 10 radicals/mg for Nrg-SLNPs, which was significantly higher than free Nrg and Nrg-SANPs. Almost 87 % reduction in oxidative stress was recorded with Nrg-SLNPs in a stress-induced lymphocyte model. In vivo studies using the Wistar rat model exhibited around 9-12-fold higher oral bioavailability of Nrg after nanoencapsulation in SLNs, as determined by high-performance liquid chromatography (HPLC). Whereas, hematological and histopathological analysis did not show any damage to the vital organs in vivo. This study presents Nrg-SLNPs as an efficient and biocompatible carrier to enhance the oral bioavailability and therapeutic activity of the natural flavonoids and warrants their further exploration in humans.
柚皮素（Nrg）是最丰富的天然膳食类黄酮，具有可观的抗炎潜力。然而，由于其吸收差、生物利用度低以及无法穿越生理屏障，其治疗应用受到限制。在此，我们设计了生物相容性固体脂质纳米粒（SLNs）来克服这些挑战，并提高Nrg的口服生物利用度和治疗潜力。通过热熔包封技术，由天然脂肪酸、硬脂酸（Nrg - SANPs）或硬脂酸和月桂酸的组合作为二元纳米粒（Nrg - SLNPs）制备了负载Nrg的固体脂质纳米粒（Nrg - SLNs）。优化后的负载Nrg的纳米粒中，SANPs的流体动力学直径为74 nm，SLNPs为91 nm，ζ电位为 - 25 mV至 - 37 mV，包封率在79%至85%之间。电子顺磁共振（EPR）光谱表明，Nrg - SLNPs的体外自由基保护因子（RPF）为215±2×10自由基/毫克，显著高于游离Nrg和Nrg - SANPs。在应激诱导的淋巴细胞模型中，Nrg - SLNPs使氧化应激降低了近87%。使用Wistar大鼠模型进行的体内研究表明，通过高效液相色谱（HPLC）测定，Nrg在纳米包封于SLNs后口服生物利用度提高了约9 - 12倍。同时，血液学和组织病理学分析未显示体内重要器官有任何损伤。本研究表明Nrg - SLNPs是一种有效且生物相容的载体，可提高天然类黄酮的口服生物利用度和治疗活性，值得在人体中进一步探索。
