University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.
R&D, PLIVA Croatia Ltd, TEVA Group Member, Zagreb, Croatia.
Int J Pharm. 2017 Nov 30;533(2):480-487. doi: 10.1016/j.ijpharm.2017.05.065. Epub 2017 May 31.
In this study, we suggest the development of nanoparticle loaded in situ gelling system suitable for corticosteroid nasal delivery. We propose lipid/alginate nanoparticles (size 252.3±2.4nm, polydispersity index 0.241, zeta-potential -31.7±1.0mV, dexamethasone (Dex) content 255±7μgml) dispersed in pectin solution (5mgml) that undergoes a sol-gel phase transition triggered by Ca present in nasal mucosa. The viscoelasticity of gel obtained by mixing nanoparticle suspension in pectin continuous phase with simulated nasal fluid (1:1V/V) is characterised by a log-linear shear thinning viscosity behaviour. Observed viscosity corresponds to the range of viscosities of nasal mucus at physiological as well as under disease conditions. Nanoparticle-loaded gel was biocompatible with the selected epithelial cell model and, in comparison to dexamethasone solution, provided reduction in Dex release (t 2.1h and 0.6h, respectively) and moderated transepithelial permeation in vitro (P 7.88±0.15 and 9.73±0.57×10cms, respectively). In conclusion, this study showed the potential of the proposed system to provide local therapeutic effect upon administration of a lower corticosteroid dose and minimize the possibility for adverse effects as it can be easily sprayed as solution and delivered beyond nasal valve, ensure prolonged contact time with nasal mucosa upon gelation, and moderate corticosteroid release and permeation.
在这项研究中，我们建议开发适合皮质类固醇鼻腔给药的载药纳米粒原位凝胶系统。我们提出将脂质/藻酸钠纳米粒（粒径 252.3±2.4nm，多分散指数 0.241，Zeta 电位-31.7±1.0mV，地塞米松（Dex）含量 255±7μgml）分散在果胶溶液（5mgml）中，该溶液在鼻黏膜中存在的 Ca 触发下发生溶胶-凝胶相转变。通过将纳米粒混悬液与模拟鼻液（1:1V/V）混合在果胶连续相中得到的凝胶的粘弹性通过对数线性剪切变稀粘度行为进行表征。观察到的粘度对应于生理条件以及疾病条件下鼻粘液的粘度范围。载药凝胶与所选上皮细胞模型具有生物相容性，与地塞米松溶液相比，载药凝胶减少了 Dex 的释放（t 2.1h 和 0.6h），并适度调节了体外跨上皮渗透（P 7.88±0.15 和 9.73±0.57×10cms，分别）。总之，这项研究表明，所提出的系统具有提供局部治疗效果的潜力，同时可以使用较低剂量的皮质类固醇，并且可以最大程度地减少不良反应的可能性，因为它可以很容易地作为溶液喷雾给药，并且可以输送到鼻阀之外，在凝胶形成时可以确保与鼻黏膜的长时间接触，并适度控制皮质类固醇的释放和渗透。
