Lipid-based nano-formulation platform for eplerenone oral delivery as a potential treatment of chronic central serous chorioretinopathy: in-vitro optimization and ex-vivo assessment.

PURPOSE: Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist used for treatment of chronic central serous chorioretinopathy which characterized by accumulation of subretinal fluid causing a localized area of retinal detachment. unfortunately, EPL suffers from poor oral bioavailability due to poor aqueous solubility in addition to high hepatic first pass metabolism.

METHOD: Aiming to improve its oral bioavailability, EPL-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification solvent evaporation method and in-vitro evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). A D-optimal design was used for study the effect of liquid lipid to solid lipid ratio, surfactant type and percentage on PS, PDI, EE%, and for data optimization. The optimized EPL-loaded NLCs system was further evaluated using in-vitro drug release and ex-vivo permeation studies through rabbit intestine in comparison to EPL aqueous suspension. The physicochemical properties of the drug in the optimized system were further examined using FT-IR and X-ray diffraction studies.

RESULTS: The resultant NLCs showed small PS (100.85-346.60 nm), homogenous distribution (0.173-0.624), negatively charged particles (ZP -20.20 to -36.75 mV), in addition to EE% (34.31-70.64%). The optimized EPL-loaded NLCs system with a desirability value of 0.905 was suggested through the Design expert® software, containing liquid to solid lipid ratio (2:1) in presence of 0.43%w/v Pluronic® F127 as a surfactant. The optimized EPL-loaded NLCs system showed a PS of 134 nm and PDI of 0.31, in addition to high EE% (76 ± 6.56%w/w), and ZP (-32.37 mV). The ex-vivo permeation study showed two-fold higher drug permeation through rabbit intestine compared to that from the aqueous drug suspension after 24 h, confirming the ability of optimized EPL-loaded NLCs system as successful oral targeting delivery carrier.

CONCLUSION: Our results pave the way for a new oral nanotherapeutic approach toward CSCR treatment. In-vivo study is currently under investigation.