Wang Xiangxiang, Xiong Haixia, Zhang Peili, Liu Ya, Gao Chang, Zhou Zhimin, Sun Jianjun, Diao Mingfang
Department of Otolaryngology, School of Medicine, South China University of Technology, Guangzhou 510006, China; Department of Endoscopic Ear Surgery, Senior Department of Otorhinolaryngology Head and Neck Surgery, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China.
Department of Endoscopic Ear Surgery, Senior Department of Otorhinolaryngology Head and Neck Surgery, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China; National Clinical Medical Research Center for Otolaryngology Diseases, Beijing 100048, China.
Colloids Surf B Biointerfaces. 2023 Mar;223:113191. doi: 10.1016/j.colsurfb.2023.113191. Epub 2023 Feb 1.
Steroids (anti-inflammatory drugs) combined with antioxidants are frequently prescribed to treat cisplatin (CP)-induced hearing loss in the clinic. Compared to systemic administration of free drugs, local drug delivery systems offer better therapeutic qualities and patient compliance since they not only can bypass the blood-labyrinth barrier but also can perform sustained release. In this work, dexamethasone (DEX) and lipoic acid (LA) non-spherical microcrystals (MCs) were prepared without complicated chemical modification. Following a series of physical characterizations, including morphology, stability and injectability, dissolution and round window membrane distribution of MCs, DEX MCs, LA MCs and the simple mixture of DEX MCs + LA MCs (combination group) were administered in guinea pigs by intratympanic injection. We found that LA MCs enabled improvement of DEX absorption in the combination group compared to a single dose. In addition, no significant morphological changes or inflammatory responses were observed in cochlear tissue, indicating good biocompatibility. Finally, the combination group also demonstrated synergistic therapeutic effect for protecting hair cells against CP-induced damage. The local co delivery of DEX MCs and LA MCs offers a new strategy for the treatment of CP-induced inner ear injury since they provide sustained anti-inflammatory and antioxidant effects simultaneously.
在临床上，类固醇（抗炎药）与抗氧化剂联合使用常用于治疗顺铂（CP）引起的听力损失。与全身给药的游离药物相比，局部给药系统具有更好的治疗效果和患者依从性，因为它们不仅可以绕过血迷路屏障，还可以实现持续释放。在这项研究中，无需复杂的化学修饰即可制备地塞米松（DEX）和硫辛酸（LA）的非球形微晶（MCs）。在对MCs、DEX MCs、LA MCs以及DEX MCs + LA MCs的简单混合物（联合组）进行包括形态、稳定性、可注射性、溶解和圆窗膜分布等一系列物理表征后，通过鼓室内注射将其给予豚鼠。我们发现，与单剂量相比，联合组中LA MCs能促进DEX的吸收。此外，在耳蜗组织中未观察到明显的形态变化或炎症反应，表明其具有良好的生物相容性。最后，联合组在保护毛细胞免受CP诱导的损伤方面也表现出协同治疗作用。DEX MCs和LA MCs的局部联合给药为治疗CP诱导的内耳损伤提供了一种新策略，因为它们能同时提供持续的抗炎和抗氧化作用。
