Retinal cell-targeted liposomal ginsenoside Rg3 attenuates retinal ischemia-reperfusion injury via alleviating oxidative stress and promoting microglia/macrophage M2 polarization.

Retinal ischemia-reperfusion (RIR) injury remains a major challenge that is detrimental to retinal cell survival in a variety of ocular diseases. However, current clinical treatments focus on a single pathological mechanism, making them unable to provide comprehensive retinal protection. A variety of natural products including ginsenoside Rg3 (Rg3) exhibit potent antioxidant and anti-inflammatory activities. Unfortunately, the hydrophobicity of Rg3 and the presence of various intraocular barriers limit its effective application in clinical settings. Hyaluronic acid (HA)- specifically binds to cell surface receptors, CD44, which is widely expressed in retinal pigment epithelial cells and M1-type macrophage. Here, we developed HA-decorated liposomes loaded with Rg3, termed Rg3@HA-Lips, to protect against retinal damage caused by RIR injury. Treatment with Rg3@HA-Lips significantly inhibited the oxidative stress induced by RIR injury. In addition, Rg3@HA-Lips promoted the transition of M1-type macrophage to the M2 type, ultimately reversing the pro-inflammatory microenvironment. The mechanism of Rg3@HA-Lips was further investigated and found that they can regulateSIRT/FOXO3a, NF-κB and STAT3 signaling pathways. Together with as well demonstrated good safety profiles, this CD44-targeted platform loaded with a natural product alleviates RIR injury by modulating the retinal microenvironment and present a potential clinical treatment strategy.

Reactive oxygen species-responsive mitochondria-targeted liposomal quercetin attenuates retinal ischemia-reperfusion injury via regulating SIRT1/FOXO3A and p38 MAPK signaling pathways.

Retinal ischemia-reperfusion (RIR) injury is involved in the pathogenesis of various vision-threatening diseases. The overproduction of reactive oxygen species (ROS) is thought to be the main cause of RIR injury. A variety of natural products, including quercetin (Que), exhibit potent antioxidant activity. However, the lack of an efficient delivery system for hydrophobic Que and the presence of various intraocular barriers limit the effective retinal delivery of Que in clinical settings. In this study, we encapsulated Que into ROS-responsive mitochondria-targeted liposomes (abbreviated to Que@TPP-ROS-Lips) to achieve the sustained delivery of Que to the retina. The intracellular uptake, lysosome escape ability, and mitochondria targeting ability of Que@TPP-ROS-Lips were evaluated in R28 retinal cells. Treating R28 cells with Que@TPP-ROS-Lips significantly ameliorated the decrease in ATP content, ROS generation, and increase in the release of lactate dehydrogenase in an in vitro oxygen-glucose deprivation (OGD) model of retinal ischemia. In a rat model, the intravitreal injection of Que@TPP-ROS-Lips 24 h after inducing retinal ischemia significantly enhanced retinal electrophysiological recovery and reduced neuroinflammation, oxidative stress, and apoptosis. Que@TPP-ROS-Lips were taken up by retina for at least 14 days after intravitreal administration. Molecular docking and functional biological experiments revealed that Que targets FOXO3A to inhibit oxidative stress and inflammation. Que@TPP-ROS-Lips also partially inhibited the p38 MAPK signaling pathway, which contributes to oxidative stress and inflammation. In conclusion, our new platform for ROS-responsive and mitochondria-targeted drug release shows promise for the treatment of RIR injury and promotes the clinical application of hydrophobic natural products.

Theoretical Analysis and Determination of the Correction Factor for a Waveguide Microcalorimeter.

This paper proposes a new method for determining the correction factor of a newly developed waveguide primary power measurement system (i.e., microcalorimeter), based on the electromagnetic field theory analysis for waveguide thermal isolation section (TIS) in foil short measurement mode. The new method determines the contribution of the power dissipated within the TIS into the correction factor, in term of the physical dimensions of the TIS. Performance comparison and analysis show that the newly proposed method can significantly reduce the measurement uncertainty when evaluating the correction factor of waveguide microcalorimeters.