Emulsion-templated synthesis and in vitro characterizations of niosomes for improved therapeutic potential of hydrophobic anti-cancer drug: tamoxifen

摘要

Hydrophobic nature of anti-cancer drugs not only imparts different pharmacokinetic barriers in drug delivery, but also associates with off-target toxicity and low-dose exposure of drug at the tumor site which is subsequently responsible for the development of multi-drug resistance. This study describes a water-in-oil emulsion templated reverse-phase evaporation strategy, using Span 120 as non-ionic surfactant, for the synthesis of tamoxifen-loaded niosomes. The dicetyl phosphate and Span 120 were used to engineer niosomes for sustained drug release over 12h and improved surface morphology. The spherical niosomes were 260-300nm in size with -34.6mV zeta potential. The scanning electron microscopy revealed a rough texture on the surface of niosomes. Niosomes released the drug in first-order and sustained release pattern up to 12h. Cholesterol was embedded in the outer hydrophobic surface of niosomes, via inclusion in oil phase, to enhance the interaction with lipid bilayer of the cells. Niosomes were able to improve the cellular uptake of tamoxifen and introduced apoptosis (29%) as major mechanism of cell death as compared to necrosis (17%). DSC and XRD studies revealed the crystalline nature of the drug inside niosomes while FTIR displayed chemical stability of the drug after entrapment. After encapsulation inside niosomes, the anti-cancer activity of tamoxifen was improved up to five times with IC50 reduced from 1M to 0.2M against MCF-7 cells. Cytotoxicity and sulforhodamine B assay revealed the apoptotic cell death. The unloaded niosomes alone showed no toxicity to the cells and presented a biocompatible nanoscale delivery platform for hydrophobic anti-cancer drugs.