De Clerck Kaat, Accou Geraldine, Sauvage Félix, Braeckmans Kevin, De Smedt Stefaan C, Remaut Katrien, Peynshaert Karen
Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Ghent Research Group on Nanomedicines, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Pharmaceutics. 2022 Aug 17;14(8):1716. doi: 10.3390/pharmaceutics14081716.
The inner limiting membrane (ILM) represents a major bottleneck hampering efficient drug delivery to the retina after intravitreal injection. To overcome this barrier, we intend to perforate the ILM by use of a light-based approach which relies on the creation of vapor nanobubbles (VNBs) when irradiating photosensitizers with high intensity laser pulses. Upon collapse of these VNBs, mechanical effects can disrupt biological structures. As a photosensitizer, we explore indocyanine green (ICG) loaded nanoparticles (NPs) specifically designed for our application. In light of this, ICG liposomes and PLGA ICG NPs were characterized in terms of physicochemical properties, ICG incorporation and VNB formation. ICG liposomes were found to encapsulate significantly higher amounts of ICG compared to PLGA ICG NPs which is reflected in their VNB creating capacity. Since only ICG liposomes were able to induce VNB generation, this class of NPs was further investigated on retinal explants. Here, application of ICG liposomes followed by laser treatment resulted in subtle disruption effects at the ILM where zones of fully ablated ILM were alternated by intact regions. As the interaction between the ICG liposomes and ILM might be insufficient, active targeting strategies or other NP designs might improve the concept to a further extent.
内界膜（ILM）是玻璃体内注射后阻碍药物有效递送至视网膜的主要瓶颈。为克服这一障碍，我们打算采用一种基于光的方法来穿透ILM，该方法依赖于用高强度激光脉冲照射光敏剂时产生蒸汽纳米气泡（VNBs）。这些VNBs塌陷时，机械效应可破坏生物结构。作为一种光敏剂，我们探索专门为我们的应用设计的负载吲哚菁绿（ICG）的纳米颗粒（NPs）。有鉴于此，对ICG脂质体和PLGA ICG NPs的物理化学性质、ICG包封情况和VNB形成进行了表征。结果发现，与PLGA ICG NPs相比，ICG脂质体包封的ICG量显著更高，这在它们产生VNB的能力上得到了体现。由于只有ICG脂质体能够诱导VNB产生，因此对这类NPs在视网膜外植体上进行了进一步研究。在这里，应用ICG脂质体后进行激光治疗，导致ILM处出现细微的破坏效应，完全消融的ILM区域与完整区域交替出现。由于ICG脂质体与ILM之间的相互作用可能不足，主动靶向策略或其他NP设计可能会进一步改进这一概念。
