Microfluidic Nanoparticle Therapy
- Anthony Sandler, MD
- Lina Chakrabarti, PhD
- Priya Srinivasan, PhD
- Don Devoe, PhD (UMD)
A novel technology is proposed for the encapsulation of therapeutic agents within nearly monodisperse liposome nanocapsules as a highly promising approach to next generation targeted drug delivery. By taking advantage of the unique microscale and nanoscale physiochemical interactions that occur at the boundary between two miscible solvent flows within a microfluidic system, liposomes with mean diameters as small as 20nm will be generated with exceptionally narrow distributions. The ability to form liposomes that are both smaller and more uniform than those previously explored for therapeutic applications has important implications for the safety and efficacy of drugs encapsulated using the microfluidic technique, and is expected to offer advantages over existing liposome production methods, including reduced toxicity and more cost-effective and agile production of liposomal drug formulations. Other benefits offered by the technology include high encapsulation efficiency with minimal reagent loss, and the ability to enable efficient in-line functionalization of liposome membranes with ligands for targeted drug delivery. Project goals include the optimization of the microfluidic liposome formation process to reduce size variations to below 5% of the mean vesicle diameter. By taking advantage of the tight control afforded over liposome size, detailed relationships between liposome size and biodistribution will be investigated for the first time using nearly-monodisperse liposomes smaller than 100 nm. The microfluidic process will be extended to enable the encapsulation of hydrophilic, amphipathic, and lipophilic drug compounds. On-line decoration of the vesicles with cancer-targeting ligands will be demonstrated, together with on-line vesicle concentration and purification in a simple flow-through process. The optimized platform will be used for automated and on-demand preparation of a combination treatment, comprising an amphipathic chemotherapeutic (doxorubicin), a lipophilic EGFR inhibitor (erlotinib), and a lipophilic FGFR inhibitor (PD-173074), to be applied to a pre-clinical study of pediatric neuroblastoma.