Assessment of Efficacy and Safety Using PPAR-γ Agonist-Loaded Nanocarriers for Inflammatory Eye Diseases.
Esther MirallesChristina S Kamma-LorgerOscar DomènechLilian SosaIsidre CasalsAna-Cristina Calpena-CampmanyMarcelle Silva-AbreuPublished in: International journal of molecular sciences (2022)
Drug-loaded nanocarriers (NCs) are new systems that can greatly improve the delivery and targeting of drugs to specific tissues and organs. In our work, a PPAR-γ agonist loaded into polymeric NCs was prepared, stabilized by spray-drying, and tested in vitro, ex vivo, and in vivo (animal models) to provide a safe formulation for optical anti-inflammatory treatments. The NCs were shown to be well tolerated, and no signs of irritancy or alterations of the eye properties were detected by the in vitro HET-CAM test and in vivo Draize test. Furthermore, no signs of cytotoxicity were found in the NC formulations on retinoblastoma cells (Y-79) analyzed using the alamarBlue assay, and the transmittance experiments evidenced good corneal transparency with the formulations tested. The ocular anti-inflammatory study confirmed the significant prevention efficacy using the NCs, and these systems did not affect the corneal tissue structure. Moreover, the animal corneal structure treated with the NCs was analyzed using X-ray diffraction using synchrotron light. Small-angle X-ray scattering (SAXS) analysis did not show a significant difference in corneal collagen interfibrillar spacing after the treatment with freshly prepared NCs or NCs after the drying process compared to the corresponding negative control when inflammation was induced. Considering these results, the PPAR-γ agonist NCs could be a safe and effective alternative for the treatment of inflammatory ocular processes.
Keyphrases
- crystal structure
- drug delivery
- wound healing
- cancer therapy
- anti inflammatory
- high resolution
- oxidative stress
- optical coherence tomography
- drug release
- insulin resistance
- gene expression
- magnetic resonance imaging
- type diabetes
- magnetic resonance
- computed tomography
- drug induced
- metabolic syndrome
- cell proliferation
- cataract surgery
- smoking cessation
- electron microscopy
- optic nerve