(T1430-07-37) NanoFabTx™: A Step-by-Step Quick Screening Platform for Liposomal Drug Delivery Systems

Purpose: Novel delivery systems like liposomes and lipid nanoparticles are designed to alleviate some of the shortcomings associated with free therapeutics. More recently, lipid-based nanoparticles have been proven effective in delivering nucleic acids in addition to small molecules. However, effective utilization of the liposomal formulations depends on a robust formulation. Development of a reproducible liposomal formulation comes with challenges, and our NanoFabTx™ platform was developed to overcome these very challenges. The NanoFabTx™ platform enables rapid screening and selection of lipid-based formulations for small molecules and nucleic acid therapeutics using extrusion and more advanced microfluidics methods. 

Methods: PEGylated and cationic DOTAP lipid formulations were selected and optimized using the NanoFabTx^TM lipid mixes and microfluidics device kit and screened for small molecule and siRNA delivery, respectively. Liposome size was determined by TEM and DLS. Doxorubicin (Dox) was encapsulated in PEGylated liposomes, delivered to PC3 cells, and evaluated via cellular uptake and cell viability assays. GFP-silencing siRNA was delivered in DOTAP liposomes and transfection was evaluated via fluorescence intensity in GFP-labeled HeLa cells. The NanoFabTx^TM lipid mixes were also formulated using syringe pumps and more advanced microfluidics devices.

Results: Liposomes synthesized using the NanoFabTX™ platform were 110-130 nm and 90-100 nm for hydration/extrusion and microfluidics methods, respectively, with a PDI ranging from 0.1-0.2. The NanoFabTx^TM lipid mixes were compatible with syringe pumps and as well as advanced microfluidics devices. PEGylated liposomes loaded with Dox accumulated in the endoplasmic reticulum of PC3 cells and resulted in 60% cell death. siRNA loaded DOTAP liposomes resulted in ~40% decrease in GFP-expression compared to the untreated control after 72 hours. Two of the three siRNA sequences also resulted in a ~50% decrease in GFP-expression regardless of preparation method. These results suggest liposomes prepared by the NanoFabTx™ platform not only delivered the siRNA to the GFP-expressing HeLa cells but also effectively silenced the target gene.

Conclusion: NanoFabTx^™ lipid mixes and device kits empowers early-stage drug nanoformulation synthesis, screening, and optimization, with optimized protocols and a curated selection of lipid-based materials for drug encapsulation.

References: Hou et al. Nat Rev Mater 2021:1079-94

The NanoFabTx™ platform provides an all-in-one microfluidic solution for Nano formulations



The NanoFabTx™ drug delivery platform