Double flow focusing microfluidic-assisted based preparation of methotrexate–loaded liposomal nanoparticles: Encapsulation efficacy, drug release and stability

Abstract

This study presents a novel and facile route to produce the methotrexate (MTX) loaded liposomal particles using the double flow focusing microfluidic (double-MHFF) device in a single step process. The double-MHFF design, due to the intensification of the mass diffusion by increasing the diffusion surface area of both phases can be a good candidate to produce the drug-loaded PEGylated liposomes. The physicochemical characteristics of the prepared MTX-liposome (MTX-L) and MTX-PEGylated liposome (MTX-PLL) such as particle size, polydispersity (PDI), and encapsulation efficiency are optimized by adjusting the operational and formulation parameters, like flow rate ratio (FRR), total flow rate (TFR), total lipid concentration and MTX concentration. Also, the release study is performed for MTX-L and MTX-PLL particles. The range of average size of the MTX-L and MTX-PLL nanoparticles are within 90–230 nm and 118–258 nm with PDI ≤ 0.32 and PDI ≤ 0.23, respectively. The double-MHFF device has the ability for achieving high encapsulation efficiency (≥ 60 %), especially for MTX-PLL. Also, the MTX-PLL nanoparticles have a sustained release and long-term fashion up to 72 h (≤ 48 %). This means that the high encapsulation efficiency and low release of MTX result from the production process.