Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.
Susbin Raj WagleBozica KovacevicCorina Mihaela IonescuThomas FosterPatrick LimAlicia BrunetSamuel McLenachanLivia CarvalhoMomir MikovArmin MooranianHani-Al SalamiPublished in: Molecular pharmaceutics (2024)
Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions. This study uses formulation-based spray dry encapsulation technology to develop polymer-based PB-lithocholic acid (LCA) nanoparticles and assesses their efficacy in the 661W photoreceptor-like cell line. Incorporating LCA enhances nanoparticles' biological efficacy without compromising PB stability. In vitro studies demonstrate that PB-LCA nanoparticles prevent reactive oxygen species (ROS)-induced oxidative stress by improving cellular viability through the nuclear erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. These findings propose PB-LCA nanoparticles as a promising therapeutic strategy for oxidative stress-induced retinopathies.
Keyphrases
- oxidative stress
- heavy metals
- induced apoptosis
- reactive oxygen species
- optical coherence tomography
- aqueous solution
- dna damage
- diabetic retinopathy
- risk assessment
- ischemia reperfusion injury
- diabetic rats
- cell death
- walled carbon nanotubes
- optic nerve
- hydrogen peroxide
- endoplasmic reticulum stress
- anti inflammatory
- signaling pathway
- case control