One-Step Fabrication of Layer-By-Layer Nanoparticles for Co-Delivery of an Anticancer Drugs Using Microfluidic Chip

With the unique structure of Layer-by-Layer (LbL) nanoparticles that can be used as multi-compartment nanosystem. LbL nanoparticles platform has been developed through controlling layer-by-layer system using fluidic nanoprecipitation and deposition process to co-deliver three chemotherapeutic agents with different physicochemical properties to challenge highly aggressive types of cancer. A newly designed microfluidic chip was fabricated which capable of assembled biocompatible LbL polymeric nanoparticles comprised of different FDA-approved polymer; poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol)–block–poly(propylene glycol)–block–poly(ethylene glycol) (Pluronic) and butylmethacrylate-dimethylaminoethylmethacrylate-methylmethacrylate copolymer (Eudragit E). The microfluidic chip with four inlets was consisted of one inlet for each polymeric solution and the last inlet as precipitating solution. The system provided a one-step approach for production of LbL polymeric nanoparticles with a consistent particle size and continuous production system. To the best of our knowledge, this is the first microfluidic chip assembled a biocompatible LbL nanoparticles that loaded with a hydrophobic drugs and a hydrophilic drug. Several process parameters and material attributes were optimized like each solution flow rate, each solution drug and polymer concentrations, and the evaporation of organic solvent. The LbL nanoparticles composed of a core and two shell layers. A nanosized core composed of pluronic as amphiphilic polymer of 112.1±10.48nm and -16.9±3.1mV. The first shell layer was assembled by forcing PLGA solution toward a stream of Pluronic core to form w/o emulsion. The formed Core/Shell nanoparticles were 215.3±14.6nm and -25.5±4.6mV. The negatively charged Core/Shell nanoparticles was inserted into aqueous Eudragit solution stream which allowed the deposition of positively charged Eudragit to negatively charged Core/Shell nanoparticles. 292.3±4.6nm and +5.5±1.6mV LbL nanoparticles were formed.