载利托那韦固体脂质纳米粒的处方、优化及体外渗透研究
Formulation, Optimization, and Ex vivo Permeation Study of Ritonavir-loaded Solid Lipid Nanoparticles.
作者信息
Guptha Prathap Madeswara, N Palei Narahari, Vijayaraj Surendran, Mohanta Bibhash Chandra, Murugesan Vanangamudi
机构信息
Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India.
Department of Pharmaceutical Sciences, Vignan's Foundation for Science, Technology, and Research (Deemed to be University), Guntur, India.
出版信息
Curr Pharm Des. 2025 Feb 25. doi: 10.2174/0113816128329768241230071303.
BACKGROUND
Ritonavir (RTV) is an antiviral drug that prevents human immunodeficiency virus (HIV). However, it has low bioavailability, which can be improved with the assistance of Solid Lipid Nanoparticles (SLNs).
OBJECTIVE
The present work aimed to formulate and optimize RTV-loaded SLNs using Box-Behnken design and evaluate the permeability coefficient using ex vivo permeation studies.
METHODS
RTV-SLNs were prepared using the ultrasonication technique. The SLN formulation was optimized based on particle size, % entrapment efficiency, and % cumulative drug release using response surface methodology resulting from Box-Behnken design. The Fourier-Transform Infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and transmission Electron Microscopy (TEM) studies were carried out for the characterization of optimized SLN formulation. Ex vivo permeation studies were also performed using chicken ileum.
RESULTS
The optimized RTV-SLNs had a particle size of 270.34 nm, polydispersity index of 0.157, and zeta potential of -25.2 mV. The % entrapment efficiency and % cumulative drug release were found to be 94.33% and 67.13%, respectively. The FT-IR study revealed that SLNs showed no significant interactions between the drug and lipid in the formulation. The % crystalline index of the RTV-loaded SLN formulation was found to be 44.31% compared to the reference value of 100% for lipids. TEM analysis showed spherical nanoparticles that were uniform in shape. The release kinetics data demonstrated the drug release behavior, followed by the Korsmeyer-Peppas model, and suggested that the release from SLNs followed the non-fiction diffusion. The permeability coefficient of optimized SLN formulation was found to be significantly (p < 0.05) more compared to free RTV suspension. The enhancement ratio results suggested that RTV-SLNs permeated significantly (p < 0.05) faster (approximately 3.5 times) as compared to free RTV suspension.
CONCLUSION
The optimized RTV-SLNs could be a promising carrier for improving the oral bioavailability of RTV.
背景
利托那韦（RTV）是一种预防人类免疫缺陷病毒（HIV）的抗病毒药物。然而，其生物利用度较低，可借助固体脂质纳米粒（SLNs）加以改善。
目的
本研究旨在采用Box-Behnken设计法制备并优化载有利托那韦的固体脂质纳米粒，并通过体外渗透研究评估其渗透系数。
方法
采用超声技术制备利托那韦固体脂质纳米粒。基于Box-Behnken设计产生的响应面法，根据粒径、包封率和药物累积释放率对固体脂质纳米粒制剂进行优化。利用傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）和透射电子显微镜（TEM）研究对优化后的固体脂质纳米粒制剂进行表征。还使用鸡回肠进行了体外渗透研究。
结果
优化后的利托那韦固体脂质纳米粒粒径为270.34 nm，多分散指数为0.157，ζ电位为-25.2 mV。包封率和药物累积释放率分别为94.33%和67.13%。FT-IR研究表明，固体脂质纳米粒制剂中的药物与脂质之间无显著相互作用。与脂质的参考值100%相比，载有利托那韦的固体脂质纳米粒制剂的结晶指数为44.31%。TEM分析显示为形状均匀的球形纳米颗粒。释放动力学数据表明了药物释放行为，符合Korsmeyer-Peppas模型，表明从固体脂质纳米粒中的释放遵循非虚构扩散。与游离利托那韦悬浮液相比，优化后的固体脂质纳米粒制剂的渗透系数显著更高（p < 0.05）。增强率结果表明，与游离利托那韦悬浮液相比，利托那韦固体脂质纳米粒的渗透速度显著更快（p < 0.05）（约3.5倍）。
结论
优化后的利托那韦固体脂质纳米粒有望成为提高利托那韦口服生物利用度的载体。
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