Tiny dexamethasone palmitate nanoparticles for intravitreal injection: optimization and in vivo evaluation.

Abstract

Tiny nanoparticles of dexamethasone palmitate (DXP) were designed as transparent suspensions for intravitreal administration to treat age-related macular degeneration (AMD). The influence of three surfactants (PEG-40-stearate and Pluronic block copolymers F68 and F127) on nanoparticles size and stability was investigated and led to an optimal formulation based on Pluronic F127 stabilizing DXP nanoparticles. Size measurements and TEM revealed tiny nanoparticles (around 35 nm) with a low opacity, compatible with further intravitreal injection. X-Ray powder diffraction (XRPD) and transmission electronic microscopy (TEM) performed on freeze-dried samples showed that DXP nanoparticles were rather monodisperse and amorphous. The efficacy of DXP nanoparticles was assessed in vivo on pigmented rabbits with unilateral intravitreal injections. After breakdown of the blood-retinal barrier (BRB) induced by injection of rhVEGF165 with carrier protein, DXP nanoparticles induced a restoration of the BRB 1 month after their intravitreal injection. However, their efficacy was limited in time most probably by clearance of DXP nanoparticles after 2 months due to their small size.