Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös str. 6., H-6720 Szeged, Hungary.
Faculty of Science and Informatics, Department of Applied & Environmental Chemistry, University of Szeged, H-6720 Szeged, Rerrich B. sq. 1., Hungary.
Eur J Pharm Sci. 2021 Nov 1;166:105960. doi: 10.1016/j.ejps.2021.105960. Epub 2021 Jul 31.
Our study aimed to formulate a novel dexamethasone (DXM)-loaded, mixed polymeric micelle-based drug delivery system, focusing on the auspicious nose-to-brain pathway, as a key delivery route to treat central nervous system (CNS) associated diseases. Polymeric micelles might be a solution to deliver drugs to the place of action compared to conventional formulations. Due to low Z-average (89.92 ± 2.7 nm), a polydispersity index of 0.216 ± 0.014 and high surface polarity (52.23%), a significant increase in water solubility (14-fold) was experienced. This increase resulted in favourable dissolution profile at nasal and axonal conditions with high in vitro permeability value (14.6×10 cm/s) on polar brain (porcine) lipid extract. Modified Side-bi-side® type diffusion study confirmed rapid and efficient passive diffusion through the nasal mucosa contributed by strong mucoadhesive properties. The final formulation met all the requirements of a nasal drug delivery system with rapid onset of action, meaning DXM can reach the CNS and there it can exert its beneficial effects in pathological conditions.
我们的研究旨在开发一种新型的地塞米松（DXM）负载的混合聚合物胶束给药系统，重点关注有利的鼻脑途径，作为治疗中枢神经系统（CNS）相关疾病的关键给药途径。与传统制剂相比，聚合物胶束可能是将药物递送到作用部位的一种解决方案。由于低 Z 均（89.92±2.7nm）、低多分散指数（0.216±0.014）和高表面极性（52.23%），药物的水溶性显著增加（14 倍）。这一增加导致在鼻和轴突条件下具有有利的溶解特性，在极性脑（猪）脂提取物上具有高体外渗透性值（14.6×10 cm/s）。经改良的 Side-bi-side® 型扩散研究证实，通过鼻黏膜的快速、高效的被动扩散与强大的黏膜黏附特性有关。最终的制剂符合鼻用药物传递系统的所有要求，具有快速起效的特点，这意味着 DXM 可以到达 CNS，并在病理条件下发挥其有益作用。
