Abstract
Purpose :
In the face of a global aging population and the increasing prevalence of age-related macular degeneration (AMD), a condition that gradually diminishes vision, there is a demand for innovative therapeutic strategies. In this study, we have developed Indomethacin (IMC)-loaded mesoporous melanin nanoparticles (IMC- loaded mMNPs) as a drug delivery carrier for the treatment of AMD. This approach has the potential to achieve synergistic therapeutic effects by combining the antioxidant properties of melanin with the anti-inflammatory activity of IMC, thereby relieving pathological damages associated with AMD.
Methods :
We introduced IMC drug onto mesoporous melanin nanoparticles (mMNPs) for its anti-inflammatory activity using EDC/NHS coupling. The size, shape, charge, and loading capacity were demonstrated through various analytical methods, including TEM, DLS, and UV-vis. We assessed the cell cytotoxicity and antioxidative properties of ICM-loaded mMNPs in an LPS-induced oxidative stress and inflammatory activity in vitro model, employing DCFDA and CCK8 assays. To evaluate the therapeutic effects of IMC-loaded mMNPs in a laser induced CNV mouse model, we performed Fundus, OCT, and immunocytochemistry analyses.
Results :
The morphology of the mesoporous structure on melanin nanoparticles with uniform spherical shapes averaging approximately 148 nm was clearly revealed through TEM images. We observed that mMNPs effectively scavenged intracellular ROS production, and cell viability after LPS-induced inflammatory activity was above 80 % in the IMC-mMNPs-treated group. Furthermore, to examine the therapeutic effects in a laser-induced CNV mouse model, we injected IMC-loaded mMNPs though a single-intravitreal administration. The Fundus/OCT and DCF staining images showed that the IMC-loaded mMNPs-injected group significantly alleviated inflammatory levels and ROS generation.
Conclusions :
IMC-loaded mMNPs were designed to fully utilize the advantageous properties of melanin and an anti-inflammatory drug for the treatment of pathological damages in AMD. Our findings demonstrate that IMC-loaded mMNPs can serve as an antioxidant and an anti-inflammatory agent, providing a potentially powerful treatment option for AMD patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.