Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo
Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo
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DOI：
10.1038/s41598-019-52069-w
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发表时间：
2019-10-29
影响因子：
4.6
通讯作者：
Kim, Ki Hean
中科院分区：
文献类型：
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作者：
Jegal, Uk;Lee, Jun Ho;Kim, Ki Hean
加替沙星是临床用于治疗眼部感染的第四代氟喹诺酮类抗生素。加替沙星的一个局限性是角膜穿透性相对较差，增加经角膜给药有助于减少每日给药的量或频率。在本研究中，采用超声治疗来增强加替沙星经角膜传递而不造成损伤。在离体和体内条件下对小鼠眼睛进行了实验。频率为1 MHz，强度为1.3W/cm(2)的超声作用于小鼠角膜5分钟，然后滴入加替沙星眼液，静置10分钟。利用加替沙星的固有荧光特性，采用双光子显微镜（TPM）成像技术测量其在角膜内的三维分布。超声处理小鼠角膜纵向TPM成像显示，初始加替沙星在角膜表面的强度比未处理小鼠角膜增加67%，随后加替沙星从角膜表面进入角膜的量增加。超声治疗组的角膜上皮内加替沙星停留时间比未治疗组长。超声治疗加替沙星在小鼠角膜内经角膜传递能力增强，停留时间延长，有利于提高治疗效果。本研究展示了超声治疗增强经角膜加替沙星给药的详细过程。
Gatifloxacin is a 4th generation fluoroquinolone antibiotic used in the clinic to treat ocular infection. One limitation of gatifloxacin is its relatively poor corneal penetration, and the increase of its transcorneal delivery would be beneficial to reduce the amount or frequency of daily dose. In this study, ultrasound treatment was applied to enhance the trans-corneal delivery of gatifloxacin without damage. Experiments were conducted on mouse eyes in ex vivo and in vivo conditions. Ultrasound waves with 1 MHz in frequency, 1.3W/cm(2) in intensity were applied onto the mouse cornea for 5 minutes, and then gatifloxacin ophthalmic solution was instilled and left there for 10 minutes. 3D gatifloxacin distribution in the cornea was measured by two-photon microscopy (TPM) imaging based on its intrinsic fluorescence. Longitudinal TPM imaging of ultrasound treated mouse corneas showed the increase of initial gatifloxacin intensities on the corneal surface compared to untreated mouse corneas by 67%, and then the increased gatifloxacin delivery into the cornea from the surface at later time. The delivered gatifloxacin in the corneal epithelium stayed longer in the ultrasound treated corneas than in the untreated corneas. The enhanced trans-corneal delivery and extended stay of gatifloxacin in the mouse cornea by ultrasound treatment could be beneficial for therapeutic effects. This study demonstrated the detail process of enhanced trans-corneal gatifloxacin delivery by ultrasound treatment.