Velentza-Almpani Angeliki, Ibeanu Nkiruka, Liu Tianyang, Redhead Christopher, Tee Khaw Peng, Brocchini Steve, Awwad Sahar, Bouremel Yann
Optceutics Ltd., 28a Menelik Road, London NW2 3RP, UK.
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Pharmaceutics. 2022 Jun 15;14(6):1267. doi: 10.3390/pharmaceutics14061267.
New in vitro prototypes (PK-Eye™) were tested with and without eye movement to understand diffusion and convection effects on intraocular clearance. Port placement in front ((i) ciliary inflow model) and behind the model lens ((ii) posterior inflow model) was used to study bevacizumab (1.25 mg/50 µL) and dexamethasone (0.1 mg/100 µL) in phosphate-buffered saline (PBS, pH 7.4) and simulated vitreal fluid (SVF). Dexamethasone was studied in a (iii) retinal-choroid-sclera (RCS) outflow model (with ciliary inflow and two outflow pathways). Ciliary vs. posterior inflow placement did not affect the half-life for dexamethasone at 2.0 µL/min using PBS (4.7 days vs. 4.8 days) and SVF (4.9 days with ciliary inflow), but it did decrease the half-life for bevacizumab in PBS (20.4 days vs. 2.4 days) and SVF (19.2 days vs. 10.8 days). Eye movement only affected the half-life of dexamethasone in both media. Dexamethasone in the RCS model showed approximately 20% and 75% clearance from the RCS and anterior outflows, respectively. The half-life of the protein was comparable to human data in the posterior inflow model. Shorter half-life values for a protein in a ciliary inflow model can be achieved with other eye movements. The RCS flow model with eye movement was comparable to human half-life data for dexamethasone.
新型体外原型（PK-Eye™）在有眼动和无眼动情况下进行了测试，以了解扩散和对流对眼内清除率的影响。在磷酸盐缓冲盐水（PBS，pH 7.4）和模拟玻璃体液（SVF）中，通过将端口放置在模型前方（(i)睫状体流入模型）和模型晶状体后方（(ii)后方流入模型）来研究贝伐单抗（1.25 mg/50 µL）和地塞米松（0.1 mg/100 µL）。地塞米松在(iii)视网膜-脉络膜-巩膜（RCS）流出模型（伴有睫状体流入和两条流出途径）中进行了研究。使用PBS（4.7天对4.8天）和SVF（睫状体流入时为4.9天）时，睫状体与后方流入位置对2.0 µL/分钟流速下地塞米松的半衰期没有影响，但确实降低了PBS（20.4天对2.4天）和SVF（19.2天对10.8天）中贝伐单抗的半衰期。眼动仅影响两种介质中地塞米松的半衰期。RCS模型中的地塞米松分别从RCS和前向流出中清除约20%和75%。该蛋白的半衰期与后方流入模型中的人体数据相当。通过其他眼动可在睫状体流入模型中实现蛋白更短的半衰期值。有眼动的RCS流动模型与地塞米松的人体半衰期数据相当。
