Formulation, Evaluation, Factorial Optimization, and In-Silico Study of Eplerenone Loaded Pectin Nanoparticles: A New Approach to the Proliferation of Human Skin Fibroblasts for Wound Healing.

Objective: Repurposing Eplerenone (EPL) for wound healing through in silico molecular docking to explore its therapeutic potential beyond its traditional use (antihypertensive drug). In this study, for a first time we investigated the potential of EPL- loaded pectin nanoparticles to enhance human skin proliferation. Methods: Ionotropic gelation method was used for preparing these EPL-loaded PN using calcium chloride as a cross-linker. Design® Expert software was used to utilize a full factorial 2³ design, where the selected factors were the pectin concentration (X₁), EPL amount (X₂), and pectin: calcium chloride concentration (X₃). The selected responses were the EPL entrapment efficiency percentage, particle size and zeta potential for determining the optimum formula for further studies such as in-vitro release studies, transmission electron microscopy (TEM), X-ray diffraction, cell culture study and in-vitro evaluation on human skin fibroblast proliferation cell. Results: The selected system demonstrated high entrapment efficiency (80.56 ± 0.62%), a particle size of 509.1 ± 45.5 nm, and good zeta potential value (-21.73 ± 2.1 mV). A spherical morphology with no aggregation using TEM and amorphization of the crystalline drug in X-ray diffraction were obtained. The Sulfo-Rhodamine B assay was applied for its effect on cell viability on human skin cells, and the selected concentration was 50 μg/mL. Conclusions: The wound healing assay on human skin fibroblasts using scratch wound technique showed the superiority of EPL on wound healing; suggesting its promising effect in enhancing skin healing and tissue regeneration. Moreover, pectin activity as a wound healing accelerator, promoting a synergistic effect. [ABSTRACT FROM AUTHOR]