Formulation Development and In vitro Characterization of Nanoparticles of Pazopanib for Wet Macular Degeneration

Document Type

Article

Publication Date

1-7-2026

Abstract

Introduction: One of the primary causes of severe vision loss globally is age-related macular degeneration (AMD), and the mainstay of therapies for neovascular diseases is intravenous administration of anti-VEGF (vascular endothelial growth factor) drugs. The goal of this research is to create an effective delivery of anti-VEGF drugs to overcome the challenges associated with current therapy and adverse effects arising from repetitive intravitreal injections.

Methods: Pazopanib (PZ) nanoparticles (NPs) have been generated to deliver the anti-VEGF drug to the posterior segment of the eye over an extended period via intravitreal injection. They were subsequently investigated for physicochemical and in vitro studies.

Results: The PZ NPs were found to be nano-sized with a particle size of 132.1 ± 1.4 nm and a PDI of 0.125 ± 0.023. The results showed that the zeta potential was -20.12 ± 2.7 mV and the entrapment efficiency was 33.9 ± 2.5%. Up to seven days of controlled drug release was observed in an in vitro drug release study. The PZ NPs were further assessed for cell cytotoxicity, cellular uptake, and anti- VEGF assays in in vitro cell culture investigations employing human retinal pigment epithelium cells (ARPE-19). In vitro cell culture tests revealed that, in comparison to the drug solution, the PZ NPs formulation was well taken up by the cells and less cytotoxic, as well as exhibited greater antiangiogenic efficacy by inhibiting VEGF expression for an extended period of time.

Discussion: The NPs demonstrated sustained drug release, driven by their controlled degradation kinetics. Increased potential intensity enhanced electrostatic repulsion, thereby improving NP stability. The low entrapment efficiency of PZ in the NPs was likely due to drug diffusion during emulsification and poor compatibility with the hydrophilic polymer matrix. For in vitro studies, ARPE-19 cells were selected due to their retinal pigment epithelial (RPE)-like properties, making them suitable for AMD drug testing. Efficacy (ELISA) assessments revealed that NP formulations had a stronger inhibitory effect than free drug solutions.

Conclusion: The proposed PZ NPs were successfully developed, characterized, and demonstrated potential application in the treatment of AMD.

DOI

https://doi.org/10.2174/0115672018385478251124140833

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