Abstract
Purpose:
To examine the neuroprotective effect of α2-agonist brimonidine loaded human serum albumin (HSA) nanoparticles on the survival of retinal ganglion cells after acute optic nerve crush.
Methods:
Brimonidine loaded HSA nanoparticles were fabricated by desolvation technique. The size distribution and zeta potential were evaluated by dynamic light scattering method. The loaded amount and in vitro release rate of brimonidine from the HSA nanoparticles were determined with the HPLC. Acute optic nerve crush was induced by clipping the optic nerve for 60s. After optic nerve injury, brimonidine loaded HSA nanoparticles, free HSA nanoparticles, and balance salt solution (BSS) control were adiministered intravitreally. Retinal ganglion cell loss was evalulated by cell count in a retinal flat mount, which was visualized by the retrograde transport of rhodamin-dextran 3000. Retinal ganglion cell loss was determined 5 days post administration.
Results:
The brimonidine loaded HSA nanoparticles showed narrow size distribution and negatively charged surface to be 152.78 +/- 51.1 nm and -29.7 +/- 7.52 mV, respectively. The concentration of brimonidine in HSA nanoparticles was 214.12 μg/mL and consistently released for over 5 days. In the neuroprotection analysis, compared to the uncrush retinal ganglion cells (control group), the BSS treated group described the retinal ganglion cell loss of 66.81 +/- 4.34 % (P<0.05). However, retinal ganglion cell loss in the brimonidine - HSA nanoparticle treated group showed 26.19 +/- 5.21% (P<0.05 vs. control group) at the dose of 8.78 μg (brimonidine). Retinal ganglion cell loss was decreased more than 2 times, compared to the BSS treated group 5 days post administration.
Conclusions:
Brimonidine loaded HSA nanoparticles delivered neuroprotective glaucomatous drugs to the retina and described the neuroprotective effect on the retinal ganglion cells effectively.
Keywords: 608 nanomedicine •
615 neuroprotection