Scheper Verena, Wolf Melanie, Scholl Markus, Kadlecova Zuzana, Perrier Thomas, Klok Harm-Anton, Saulnier Patrick, Lenarz Thomas, Stöver Timo
Department of Otolaryngology, Medical University Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Nanomedicine (Lond). 2009 Aug;4(6):623-35. doi: 10.2217/nnm.09.41.
Treatment of sensorineural hearing loss could be advanced using novel drug carriers such as hyperbranched polylysine (HBPL) or lipid nanocapsules (LNCs). This study examined HBPL and LNCs for their cellular uptake and possible toxicity in vitro and in vivo as the first step in developing novel nanosized multifunctional carriers.
Having incubated HBPL and LNCs with fibroblasts, nanoparticle uptake and cell viability were determined by confocal laser scanning microscopy, fluorescence measurements and neutral red staining. In vivo, electrophysiology, confocal laser scanning microscopy and cytocochleograms were performed for nanoparticle detection and also toxicity studies after intracochlear application.
Both nanoparticles were detectable in the fibroblasts' cytoplasm without causing cytotoxic effects. After in vivo application they were visualized in cochlear cells, which did not lead to a change in hearing threshold or loss of hair cells. Biocompatibility and traceability were demonstrated for HBPL and LNCs. Thus, they comply with the basic requirements for drug carriers for potential application in the inner ear.
使用新型药物载体如超支化聚赖氨酸(HBPL)或脂质纳米囊泡(LNCs)可推动感音神经性听力损失的治疗。本研究检测了HBPL和LNCs在体外和体内的细胞摄取情况及可能的毒性,作为开发新型纳米多功能载体的第一步。
将HBPL和LNCs与成纤维细胞孵育后,通过共聚焦激光扫描显微镜、荧光测量和中性红染色来测定纳米颗粒摄取和细胞活力。在体内,进行电生理学、共聚焦激光扫描显微镜检查和细胞耳蜗电图以检测纳米颗粒,并在耳蜗内应用后进行毒性研究。
两种纳米颗粒均可在成纤维细胞胞质中检测到,且不产生细胞毒性作用。体内应用后,它们在耳蜗细胞中可见,这并未导致听力阈值改变或毛细胞损失。HBPL和LNCs表现出生物相容性和可追踪性。因此,它们符合内耳潜在应用药物载体的基本要求。