Intravitreal curcumin-loaded nanostructured lipid carriers for the management of post-traumatic proliferative vitreoretinopathy: optimization, in vitro characterization, and in vivo animal study.

Proliferative vitreoretinopathy (PVR) is a pathological vision-threatening complication that develops after a penetrating ocular trauma, retinal detachment and/or retinal reattachment surgery. After retinal break, epidermal growth factor (EGF) mediates the proliferation and dedifferentiation of retinal pigment epithelial cells (RPE) into fibrotic pre/subretinal PVR membranes. The contraction of these membranes results in tractional retinal detachment. To date, there is no approved adjuvant treatment for the prevention of PVR recurrence after surgical peeling of the membranes, and few studies have reported improved clinical outcomes with investigational therapies. Curcumin, a polyphenol compound, is suggested to downregulate EGF expression and prevent RPE proliferation. Driven by these facts, this work explores the potential utility of intravitreal sustained release curcumin-loaded nanostructured lipid carriers (CUR-NLCs) as an adjuvant treatment for post-traumatic PVR in a rabbit model. CUR-NLCs were prepared using a hot melt emulsification/ultrasonication technique. The formulation variables were studied using a three-factor Box-behnken design (BBD), and combined desirability function was applied to optimize the formulation. Optimized CUR-NLCs exhibited spherical morphology and had a mean particle size of 65.54 ± 1.28 nm, a zeta-potential of -19.5 ± 4.30 mV, and an entrapment efficiency of 73.79 ± 3.25%. The in vitro release study showed diffusion-dependent CUR release of 43.18 ± 0.93% over 72 h. In vivo animal study revealed that CUR-NLCs appear to have asubstantial clinical/biological effecton reducing fibrous proliferation and PVR grades in rabbit eyes with a large effect size (ε2 = 0.356) though non statistically significant (exact p = 0.146). These results highlight the beneficial effect of CUR-NLCs on reducing the severity of trauma-associated PVR.