Preparation of lipid-based drug delivery systems by microfluidics has been increasingly popular, due to the reproducible, continuous and scalable nature of the microfluidic process. Despite exciting development in the field, versatility and superiority of microfluidics over conventional methods still need further evidence, since preparing clinically-relevant sterically stabilised liposomes has been lacking. The present study describes the optimisation of PEGylated liposomal formulations of various rigidity using staggered herringbone micromixer (SHM). The effect of both processing parameters (total flow rate (TFR) and aqueous-to-ethanol flow rate ratio (FRR)) and formulation parameters (lipid components and composition, initial lipid concentration and aqueous media) was investigated and discussed. Liposomal formulations consist of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), with cholesterol and PEGylated lipid (DSPE-PEG2000) were successfully prepared with the desired size (∼100 nm) and dispersity (< 0.2). Doxorubicin was successfully encapsulated in these liposomes at high (> 80%) encapsulation efficiency using the pH-gradient remote loading method, illustrating their bilayer integrity and capability as drug delivery systems. We demonstrated that clinically-relevant PEGylated liposomal formulations could be prepared with properties comparable to conventional techniques. Limitations and recommendations on the microfluidic production of PEGylated liposomes were also discussed.
Bibliographical noteCopyright © 2019. Published by Elsevier B.V.
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Student thesis: Doctoral Thesis › Doctor of PhilosophyFile