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

Abstract

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.

Cod liver oil nano-structured lipid carriers (Cod-NLCs) as a promising platform for nose to brain delivery: Preparation, in vitro optimization, ex vivo cytotoxicity & in vivo biodistribution utilizing radioiodinated zopiclone

“…This difference in hydrophobicity allows their orientation to form micelles in the aqueous phase ( Thapa et al, 2020 ). Thus forming a rigid layer of surfactant around the formed particles, preventing drug leaking and offering better drug housing and so better drug EE% ( Abdelhakeem et al, 2021 ). These results came in agreement with the results found by Zafar et al ( Zafar et al, 2022 ) who prepared NLCs-based erythromycin gel and revealed that the increase of Pluronic F127 (poloxamer 407) from 2% to 5% was accompanied by an increase in EE %.…”

Preparation of NLCs-Based Topical Erythromycin Gel: In Vitro Characterization and Antibacterial Assessment

“…They are also reported for high drug load without drug leakage [ 5 ], which enhances drug release and bioavailability [ 11 ]. Various studies published on ocular NLCs report a high corneal contact time in comparison to pure drug solution [ 5 , 12 , 13 , 14 ]. They report a significant enhancement in corneal permeation and a decrease in ocular clearance.…”

Novel Bioactive Extraction and Nano-Encapsulation

“…These encapsulated bioactive compounds reflected slower release due to slower erosion of lipid wall matrix (12 h). Another study conducted by Abd-Elhakeem et al [139] illustrated about improving the bioavailability and oral target delivery of eplerenone by using lipid-based nanoencapsulation. Eplerenone-loaded nano-lipid capsules reflected in improved permeability up to two folds higher compared to conventional aqueous drug in rabbit intestine after the period of 24 h.…”