PhD Program in Chemical Science and Technology, Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, via Vienna 2, 07100 Sassari, Italy.
Department of Medicine, Surgery and Pharmacy, University of Sassari, via Muroni 23a, 07100 Sassari, Italy.
Int J Biol Macromol. 2024 Oct;278(Pt 4):134908. doi: 10.1016/j.ijbiomac.2024.134908. Epub 2024 Aug 23.
Dimethyl fumarate (DMF) is a drug that is orally administered for the treatment of relapsing-remitting multiple sclerosis. However, DMF causes gastrointestinal side effects and flushing in 43 % of patients, which significantly contributes to treatment discontinuation. To reduce side effects and increase patient compliance, the aim of this study was to develop a thermosensitive chitosan/glycerophosphate hydrogel for the nasal administration of DMF. A binary system of DMF with hydroxypropyl-β-cyclodextrin (HP-β-CD) was made and included in the hydrogel precursor solution. The precursor solution (drug content, DMF stability, thermogelling properties, viscosity), and the resulting thermosensitive hydrogel (mucoadhesion, in vitro DMF permeation) were characterized. HP-β-CD was able to interact with DMF and improve its water solubility. The leader thermosensitive nasal solution, G1 solution, was loaded with approximately 92 % DMF, which remained stable for 21 days. The G1 solution formed a hydrogel in approximately 2-1 min; it had a pH of 6.8 ± 0.06 and caused no significant change in the osmolality of the simulated nasal medium. The G1 hydrogel showed good mucoadhesive properties and released DMF that permeated in vitro in a controlled manner. As a result, G1 is a potential new approach to exploit the intranasal administration of DMF for treating multiple sclerosis.
富马酸二甲酯（DMF）是一种用于治疗复发缓解型多发性硬化症的口服药物。然而，DMF 会导致 43%的患者出现胃肠道副作用和潮红，这极大地导致了治疗的中断。为了降低副作用并提高患者的顺应性，本研究旨在开发一种用于 DMF 鼻内给药的热敏壳聚糖/甘油磷酸盐水凝胶。将 DMF 与羟丙基-β-环糊精（HP-β-CD）制成二元体系，并包含在水凝胶前体溶液中。对前体溶液（药物含量、DMF 稳定性、温敏性能、粘度）和所得热敏水凝胶（黏膜黏附性、体外 DMF 渗透）进行了表征。HP-β-CD 能够与 DMF 相互作用并提高其水溶性。主导的热敏鼻溶液 G1 溶液负载了约 92%的 DMF，在 21 天内保持稳定。G1 溶液在大约 2-1 分钟内形成水凝胶；其 pH 值为 6.8±0.06，对模拟鼻介质的渗透压没有显著影响。G1 水凝胶具有良好的黏膜黏附性，并以受控方式释放体外渗透的 DMF。因此，G1 是一种利用 DMF 经鼻给药治疗多发性硬化症的新方法。
