Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
National Center for Nano Fabrication and Characterization, Technical University of Denmark, Lyngby, Denmark.
Transl Vis Sci Technol. 2023 Aug 1;12(8):20. doi: 10.1167/tvst.12.8.20.
Drug delivery to the retina remains a challenge due to ocular barriers and fast clearing mechanisms. Nanocarrier drug delivery systems (NDDSs) hold the promise of prolonging intraocular retention times and increasing drug concentrations in the retina.
Anionic and cationic PEGylated liposomes, loaded with oxaliplatin (OxPt) to be used as trace element, were prepared from dry lipid powders. The differently charged liposomes were intravitreally injected in C57BL/6JrJ mice; eyes were harvested 2 hours and 24 hours post-injection. To investigate active transport mechanisms in the eye, a subset of mice were pre-injected with chloroquine before injection with cationic liposomes. Eyes were dissected and the distribution of OxPt in different tissues were quantified by inductively coupled plasma mass spectrometry (ICP-MS).
Both liposome formulations enhanced the retention time of OxPt in the vitreous over free OxPt. Surprisingly, when formulated in cationic liposomes, OxPt translocated through the retina and accumulated in the RPE-sclera. Pre-injection with chloroquine inhibited the transport of liposomal OxPt from the vitreous to the RPE-sclera.
We show that liposomes can enhance the retention time of small molecular drugs in the vitreous and that active transport mechanisms are involved in the trans retinal transport of NDDS after intravitreal injections.
These results highlight the need for understanding the dynamics of ocular transport mechanisms in living eyes when designing NDDS with the back of the eye as the target. Active transport of nanocarriers through the retina will limit the drug concentration in the neuronal retina but might be exploited for targeting the RPE.
由于眼部屏障和快速清除机制，药物向视网膜的输送仍然是一个挑战。纳米载体药物传递系统（NDDS）有望延长眼内滞留时间并增加视网膜中的药物浓度。
从干燥的脂质粉末中制备载有奥沙利铂（OxPt）的阴离子和阳离子 PEG 化脂质体，用作微量元素。将不同带电的脂质体眼内注射到 C57BL/6JrJ 小鼠中；注射后 2 小时和 24 小时收获眼睛。为了研究眼睛中的主动转运机制，在注射阳离子脂质体之前，一部分小鼠预先注射了氯喹。通过电感耦合等离子体质谱法（ICP-MS）将眼睛解剖并定量分析 OxPt 在不同组织中的分布。
两种脂质体配方均增强了玻璃体中 OxPt 的保留时间，超过了游离 OxPt。令人惊讶的是，当用阳离子脂质体配制时，OxPt 通过视网膜转运并在 RPE-脉络膜中积累。预先注射氯喹抑制了脂质体 OxPt 从玻璃体向 RPE-脉络膜的转运。
我们表明脂质体可以增强玻璃体中小分子药物的保留时间，并且主动转运机制参与了眼内注射后 NDDS 的跨视网膜转运。
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