Tzeyung Angeline Shak, Md Shadab, Bhattamisra Subrat Kumar, Madheswaran Thiagarajan, Alhakamy Nabil A, Aldawsari Hibah M, Radhakrishnan Ammu K
School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia.
Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia.
Pharmaceutics. 2019 Jan 10;11(1):26. doi: 10.3390/pharmaceutics11010026.
The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery.
本研究的目的是开发、优化和评估用于鼻脑递送的罗替戈汀壳聚糖纳米粒（RNPs）。通过离子凝胶法制备罗替戈汀壳聚糖纳米粒，并针对壳聚糖、三聚磷酸钠、罗替戈汀浓度对粒径、多分散指数（PDI）、zeta电位和包封率等各种参数进行优化。使用光子相关光谱、透射电子显微镜、扫描电子显微镜、原子力显微镜、傅里叶变换红外光谱和X射线衍射对制备的纳米粒进行表征。所制备的RNPs显示出较小的流体动力学粒径（75.37±3.37nm）、较小的PDI（0.368±0.02）、令人满意的zeta电位（25.53±0.45mV）和非常高的包封率（96.08±0.01）。纳米粒中罗替戈汀的24小时体外释放率和离体鼻腔渗透率分别为49.45±2.09%和92.15±4.74%，而罗替戈汀溶液的相应值分别为95.96±1.79%和58.22±1.75%。与罗替戈汀溶液相比，通量和渗透系数的总体改善率分别为4.88和2.67。组织病理学研究表明，纳米粒制剂对鼻黏膜无毒性或结构损伤。我们的结果表明，罗替戈汀壳聚糖纳米粒为鼻脑递送提供了一种有效的载体。
