Span60/Cholesterol Niosomal Formulation as a Transport Vehicle for L-DOPA and Rasagiline Delivery with Potent In...

This study investigates the potential of niosomal drug delivery systems encapsulating L-DOPA and Rasagiline for Parkinson's disease treatment. The aim is to enhance neuroprotective efficacy, reduce cytotoxic and genotoxic effects, and modulate PD-related gene expression. Niosomes were prepared using varying lipid-to-drug and Span 60-to-cholesterol ratios. Characterization included morphology, particle size, polydispersity index, and surface charge using Transmission electron microscopy and Zetasizer. Drug encapsulation efficiency was measured spectrophotometrically, and in vitro release was assessed in PBS (pH 7.4). Compared to free drugs, niosome-encapsulated L-DOPA and Rasagiline exhibited significantly reduced cytotoxicity and enhanced neuroprotective effects. Cytotoxicity of free and encapsulated drugs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human dermal fibroblast cells (HDF). SH-SY5Y cells were differentiated into neuron-like cells using all-trans retinoic acid and exposed to methyl-4-phenylpyridinium (MPP+) to induce a PD model. Neuroprotective effects were assessed by comparing drug-loaded niosomes with free drugs. Genotoxicity was evaluated using Hoechst 33258 staining. Real-time quantitative polymerase chain reaction was performed to analyze PINK1 and LRRK2 gene expression. Niosomal formulations showed spherical morphology, nanoscale size, low polydispersity index, negative surface charge, high drug encapsulation, and sustained release. Drug-loaded niosomes exhibited reduced cytotoxicity in HDF cells and greater neuroprotection in MPP+-induced SH-SY5Y cells compared to free drugs, with minimal genotoxicity. PINK1 was upregulated, and LRRK2 was downregulated after treatment with the drug-loaded formulations. L-DOPA and Rasagiline-loaded niosomes demonstrated effective delivery, neuroprotection, and gene modulation with minimal toxicity. These findings demonstrate the potential of niosomal encapsulation of L-DOPA and Rasagiline in an in vitro Parkinson's disease model, and indicate the necessity for further mechanistic and in vivo investigation.