Department of Otolaryngology & Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
Small. 2022 Sep;18(36):e2106591. doi: 10.1002/smll.202106591. Epub 2022 Feb 1.
The least damaging and most economical method to deliver drugs or carriers into the inner ear for treatment of disease is through the middle ear. However, the retention of drug in the middle ear is an obstacle. Here, inspired by the adhesion of mussels, a methacrylate gelatin microspheres (GM) coupling polydopamine (PDA) layer (GM@PDA) with excellent adhesive ability is constructed, and Ebselen liposomes are further loaded into the GM@PDA (GM@PDA@Lipo-Ebselen). The loading capacity of GM@PDA for Ebselen liposomes is 25 ± 1 µg mg microspheres. GM@PDA@Lipo-Ebselen could be injected on round windows membrane (RWM) and tightly adheres to the surface of RWM by PDA, and the microspheres are even still attached to the RWM after 360° rotation and inverted shaking. The in vivo imaging system shows that the adhesive microspheres can prolong the retention of the middle ear cavity for more than 7 days. The hearing of mice in the GM@PDA@Lipo-Ebselen group is significantly recovered, especially on day 14 after noise exposure, and the hearing of each frequency is restored to baseline level. At 32 kHz frequency, the survival of outer hair cells recovers from 48 0± 6% to 93 ± 2%. Therefore, the adhesive and injectable hydrogel microspheres provide a promising strategy for the treatment of hearing loss.
将药物或载体递送至内耳以治疗疾病的最具损伤性和最经济的方法是通过中耳。然而，药物在中耳中的保留是一个障碍。在这里，受贻贝粘附的启发，构建了一种具有优异粘附能力的甲基丙烯酸明胶微球（GM）偶联聚多巴胺（PDA）层（GM@PDA），并进一步将艾布硒啉脂质体载入 GM@PDA（GM@PDA@Lipo-Ebselen）中。GM@PDA 对艾布硒啉脂质体的载药量为 25±1μgmg 微球。GM@PDA@Lipo-Ebselen 可以注射到圆窗膜（RWM）上，并且通过 PDA 紧密地粘附在 RWM 的表面上，即使在 360°旋转和倒置摇晃后，微球仍附着在 RWM 上。体内成像系统显示，粘性微球可以将中耳腔的保留时间延长超过 7 天。GM@PDA@Lipo-Ebselen 组中小鼠的听力明显恢复，尤其是在噪声暴露后 14 天，每个频率的听力均恢复到基线水平。在 32 kHz 频率下，外毛细胞的存活率从 480±6%恢复到 93±2%。因此，这种具有粘附性和可注射性的水凝胶微球为治疗听力损失提供了一种有前途的策略。
