Microfluidic methods for liposome formation

Microfluidic is an emerging technology for the preparation of liposomes. Precise control of fluid flow and mixing offers self-assembly of lipids into homogeneous liposomes with tunable sizes through simple flow rate optimization. Continuous flow and parallelization allow seamless scale-up production for meeting clinical manufacturing demands. Multifunctional microfluidic modules can be designed for in-line drug loading and purification. Microfluidic-assisted methods can also be utilized to prepare lipid-based gene delivery systems, such as RNA-delivery systems. This book chapter summarizes the state-of-the-art microfluidic technology in liposome production for drugs and biologics (proteins and nucleic acids) delivery and its applicability to clinical applications

Liposome-Templated Indocyanine Green J- Aggregates for In Vivo Near-Infrared Imaging and Stable Photothermal Heating

Indocyanine green (ICG) is an FDA-approved near-infrared fluorescent dye that has been used in optical imaging and photothermal therapy. Its rapid in vivo clearance and photo-degradation have limited its application. ICG pharmacokinetics and biodistribution have been improved via liposomal encapsulation, while its photothermal stability has been enhanced by ICG J-aggregate (IJA) formation. In the present work, we report a simple approach to engineer a nano-sized, highly stable IJA liposomal formulation. Our results showed that lipid film hydration and extrusion method led to efficient IJA formation in rigid DSPC liposomes, as supported by molecular dynamics modeling. The engineered DSPC-IJA formulation was nano-sized, and with spectroscopic and photothermal properties comparable to free IJA. Promisingly, DSPC-IJA exhibited high fluorescence, which enabled its in vivo tracking, showing prolonged blood circulation and significantly higher tumor fluorescence signals, compared to free ICG and IJA. Furthermore, DSPC-IJA demonstrated high photo-stability in vivo after multiple cycles of 808 nm laser irradiation. Finally, doxorubicin was loaded into liposomal IJA to utilize the co-delivery capabilities of liposomes. In conclusion, with both liposomes and ICG being clinically approved, our novel liposomal IJA could offer a clinically relevant theranostic platform enabling multimodal imaging and combinatory chemo- and photothermal cancer therapy.Peer reviewe