Chemical Engineering Journal, Vol.334, 1766-1774, 2018
Continuous production of antioxidant liposome for synergistic cancer treatment using high-gravity rotating packed bed
Liposome not only can be used as delivery systems for drugs, but has the ability to act as a solubilizing agent for drugs with low aqueous solubility. However, a key limitation in exploiting liposome technology is the availability of scalable, simple production methods for the preparation of liposome. Here we provide a new method, using high gravity technology, to prepare drug loaded liposome with high throughput. The effects of different variables, such as temperature, high gravity level, flow rate ratio of solvent phase to aqueous phase, the mass ratio of egg phosphatidylcholine (EPC) to cholesterol and the mass ratio of EPC to sorafenib (SFN) on particle size and the drug encapsulation efficiency were investigated using an orthogonal experimental design. Through formulation optimization, liposome with average size of 200 nm was successfully produced and drug encapsulation could reach 89%. The as-prepared SFN loaded liposome exhibited greatly enhanced drug release rate compared with the raw SFN. Moreover, resveratrol, as antioxidant, was added into the drug formulation. The addition of resveratrol in the drug formulation not only increased the anti-oxidizability and stability of the liposome but also produced synergistic anticancer effects by cytotoxicity assay.