Kim Hyeong Min, Han Hyounkoo, Hong Hye Kyoung, Park Ji Hyun, Park Kyu Hyung, Kim Hyuncheol, Woo Se Joon
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Korea.
Pharmaceutics. 2021 May 4;13(5):655. doi: 10.3390/pharmaceutics13050655.
In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time-concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the outward direction permeability of the RCS and CS and calculated the neural retina permeability. The permeability coefficients of RCS and CS were as follows: ganciclovir, 13.78 ± 5.82 and 23.22 ± 9.74; brimonidine, 15.34 ± 7.64 and 31.56 ± 12.46; bevacizumab, 0.0136 ± 0.0059 and 0.0612 ± 0.0264 (×10 cm/s). The calculated permeability coefficients of the neural retina were as follows: ganciclovir, 33.89 ± 12.64; brimonidine, 29.83 ± 11.58; bevacizumab, 0.0205 ± 0.0074 (×10 cm/s). Between brimonidine and ganciclovir, lipophilic brimonidine presented better RCS and CS permeability, whereas ganciclovir showed better calculated neural retinal permeability. The large molecular weight drug bevacizumab demonstrated a much lower permeability than brimonidine and ganciclovir. In conclusion, the ophthalmic drug permeability of RCS and CS is affected by the molecular weight and lipophilicity, and influences the intravitreal half-life.
在本研究中，通过从神经视网膜上刮下制备视网膜-视网膜色素上皮-脉络膜-巩膜（RCS）和视网膜色素上皮-脉络膜-巩膜（CS），并使用Ussing小室，我们测量了每个药物分子在五个分离的兔组织的接受室中的平均时间-浓度值。我们确定了RCS和CS的外向通透性，并计算了神经视网膜通透性。RCS和CS的通透系数如下：更昔洛韦，13.78±5.82和23.22±9.74；溴莫尼定，15.34±7.64和31.56±12.46；贝伐单抗，0.0136±0.0059和0.0612±0.0264（×10 cm/s）。计算得到的神经视网膜通透系数如下：更昔洛韦，33.89±12.64；溴莫尼定，29.83±11.58；贝伐单抗，0.0205±0.0074（×10 cm/s）。在溴莫尼定和更昔洛韦之间，亲脂性的溴莫尼定表现出更好的RCS和CS通透性，而更昔洛韦显示出更好的计算得到的神经视网膜通透性。大分子药物贝伐单抗的通透性比溴莫尼定和更昔洛韦低得多。总之，RCS和CS的眼用药物通透性受分子量和亲脂性影响，并影响玻璃体内半衰期。
