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基于β-环糊精和寡聚精氨酸肽的树枝状聚合物包裹金纳米颗粒用于改善药物向内耳的递送

β-Cyclodextrin and Oligoarginine Peptide-Based Dendrimer-Entrapped Gold Nanoparticles for Improving Drug Delivery to the Inner Ear.

作者信息

Luo Jia, Lin XueXin, Li LiLing, Tan JingQian, Li Peng

机构信息

Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Department of Otolaryngology Head and Neck Surgery, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.

出版信息

Front Bioeng Biotechnol. 2022 Apr 11;10:844177. doi: 10.3389/fbioe.2022.844177. eCollection 2022.

DOI:10.3389/fbioe.2022.844177
PMID:35480970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9038081/
Abstract

Here, we developed a safe and highly effective nanocarrier using β-cyclodextrin (β-CD) and oligoarginine peptide (Arg8)-modified dendrimer-entrapped gold nanoparticles (Au@CD-PAMAM-Arg8), with a diameter of 5 nm, for improved delivery of dexamethasone (Dex) to the inner ear. The properties and distribution of the Au@CD-PAMAM-Arg8 were assessed , and a streptomycin (SM) ototoxicity model was used . Flow cytometry analysis of HEIOC1 cells treated with Au@CD-PAMAM-Arg8 and Au @CD-PAMAM at different time intervals indicated that cell uptake efficiency of the drug delivery carrier Au@CD-PAMAM-Arg8 was higher than that of Au @CD-PAMAM. Au@CD-PAMAM-Arg8 carrying Dex (Au@CD-PAMAM-Arg8/Dex) were mainly distributed in hair cells, the spiral ganglion, lateral wall, and nerve fibers and had stronger protective effects on the inner ear than Dex administration alone. tracer tests revealed that tympanic injection was significantly more effective than posterior ear injection, muscle injection, and tail vein injection, whereas clinical retro-auricular injection could not increase the efficiency of drug delivery into the ear. Electrocochleography results showed that Au@CD-PAMAM-Arg8/Dex significantly improved hearing in C57/BL6 mice after SM exposure. These findings indicate that Au@CD-PAMAM-Arg8 may be the useful drug carriers for the treatment of inner ear diseases.

摘要

在此，我们利用β-环糊精（β-CD）和寡聚精氨酸肽（Arg8）修饰的树枝状聚合物包裹的金纳米颗粒（Au@CD-PAMAM-Arg8）开发了一种安全且高效的纳米载体，其直径为5纳米，用于改善地塞米松（Dex）向内耳的递送。评估了Au@CD-PAMAM-Arg8的性质和分布，并使用了链霉素（SM）耳毒性模型。对在不同时间间隔用Au@CD-PAMAM-Arg8和Au@CD-PAMAM处理的HEIOC1细胞进行流式细胞术分析表明，药物递送载体Au@CD-PAMAM-Arg8的细胞摄取效率高于Au@CD-PAMAM。携带地塞米松的Au@CD-PAMAM-Arg8（Au@CD-PAMAM-Arg8/Dex）主要分布在毛细胞、螺旋神经节、外侧壁和神经纤维中，并且比单独给予地塞米松对内耳具有更强的保护作用。示踪剂测试表明，鼓膜注射明显比耳后注射、肌肉注射和尾静脉注射更有效，而临床耳后注射不能提高药物递送至耳部的效率。耳蜗电图结果显示，Au@CD-PAMAM-Arg8/Dex在链霉素暴露后显著改善了C57/BL6小鼠的听力。这些发现表明，Au@CD-PAMAM-Arg8可能是治疗内耳疾病的有用药物载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/225b/9038081/d6e1a0498945/fbioe-10-844177-g009.jpg
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