University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160014, India.
UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, 160014, India.
Colloids Surf B Biointerfaces. 2021 Sep;205:111838. doi: 10.1016/j.colsurfb.2021.111838. Epub 2021 May 14.
Ferulic acid (FA) is a ubiquitous natural plant bioactive with distinctive promise in neurodegenerative disorders. However, its therapeutic efficacy gets compromised owing to its poor aqueous solubility, inadequate permeability across lipophilic barriers, and extensive first-pass metabolism. The current studies, therefore, were undertaken to systematically develop chitosan-coated solid lipid nanoparticles (SLNs) using QbD paradigms for improved efficacy of FA in the management of Alzheimer's disease (AD). SLNs of FA were formulated employing Compritol as lipid and polysorbate 80 as surfactant and optimised using a 3 Central Composite Design (CCD). The optimized formulation, surface-coated with chitosan using ionic gelation, exhibited particle size of 185 nm, entrapment efficiency of 51.2 % and zeta potential of 12.4 mV. FTIR and DSC studies verified the compatibility of FA with formulation excipients, PXRD construed significant loss of drug crystallinity, while FESEM depicted existence of uniform spherical nanoparticles with little aggregation. Notable improvement in ex vivo mucoadhesion and permeation studies using goat nasal mucosa, coupled with extension in in vitro drug release, was obtained with SLNs. Substantial improvement with SLNs in cognitive ability through the reduction in escape latency time during behavioural studies, together with significant improvement in various biochemical parameters and body weight gain was observed in AD-induced rats. Histopathological images of different rat organs showed no perceptible change(s) in tissue morphology. Overall, these preclinical findings successfully demonstrate improved anti-AD efficacy, superior nasal mucoadhesion and permeation, extended drug release, improved patient compliance potential, safety and robustness of the developed lipidic nanoconstructs of FA through intranasal route.
阿魏酸（FA）是一种普遍存在的天然植物生物活性物质，在神经退行性疾病中有独特的应用前景。然而，由于其较差的水溶性、脂溶性屏障通透性不足以及广泛的首过代谢，其治疗效果受到影响。因此，本研究采用 QbD 范式，系统地开发壳聚糖包被的固体脂质纳米粒（SLN），以提高 FA 在阿尔茨海默病（AD）治疗中的疗效。采用 Compritol 作为脂质，聚山梨醇酯 80 作为表面活性剂，采用 3 中心组合设计（CCD）进行优化，制备 FA 的 SLN。用离子凝胶法对优化后的配方进行壳聚糖表面包覆，得到粒径为 185nm、包封率为 51.2%、Zeta 电位为 12.4mV 的 SLN。傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）研究证实了 FA 与制剂赋形剂的相容性，粉末 X 射线衍射（PXRD）表明药物结晶度显著降低，而场发射扫描电子显微镜（FESEM）显示存在少量聚集的均匀球形纳米粒子。通过山羊鼻黏膜进行的体外黏附性和渗透性研究，以及体外药物释放的延长，均得到了 SLN 的显著改善。通过减少行为研究中的逃逸潜伏期时间，SLN 显著改善了 AD 诱导大鼠的认知能力，同时还显著改善了各种生化参数和体重增加。不同大鼠器官的组织学图像显示，组织形态没有明显变化。总的来说，这些临床前研究结果成功地证明了通过鼻腔给药，提高了 FA 的抗 AD 疗效、鼻腔黏附性和渗透性、延长了药物释放、提高了患者顺应性、安全性和稳健性。
