Designing of fatty acid-surfactant conjugate based nanomicelles of morin hydrate for simultaneously enhancing anticancer activity and oral bioavailability.

Abstract

Morin hydrate (MH) is a naturally occurring polyphenolic flavonol compound. It has been recently investigated for its many biological activities such as anti-inflammatory, anticancer, antioxidant, antiarthritic, antifertility, antiplasmodic and anticancer. Though these outcomes are very promising, its low aqueous solubility and oral bioavailability restrict its clinical uses. Therefore, in this study we report pluronic F68 and stearic acid conjugated (F68-SA) nanomicelles for increasing oral bioavailability of MH. The MH loaded F68-SA nanomicelles (MHNM) were prepared by the solvent evaporation method. The MHNM were extensively characterized for the size, surface charge, stability, morphology, critical micelle concentration, drug content, and in-vitro drug release. The cell viability assay depicted a significant increase in cytotoxicity of MH against A549 human lung cancer cells after incubating as MHNM. Exposure of A549 cells to MHNM induced cell apoptosis in the cells as observed in apoptosis studies. Pharmacokinetic studies in Sprague-Dawley rats revealed that MHNM significantly increased the oral bioavailability of MH as compared to pure drug. Therefore, the novel, surfactant-lipid based micellar system is an effective solubilizing and delivering system for oral administration of poorly water soluble drugs like MH.