Microfluidic synthesis of multilayered lipid-polymer hybrid nanoparticles for the formulation of low solubility drugs.

Abstract

Hybrid phospholipid/block copolymer membranes where polymers and lipids are molecularly mixed or phase-separated into polymer-rich and lipid-rich domains are promising drug delivery materials. Harnessing the chemical diversity of polymers and the biocompatability of lipids is a compelling approach to design the next generation of drug carriers. Here, we report on the development of a microfluidics-based strategy analogous to produce lipid nanoparticles (LNPs) for the nanomanufacturing of multilayered hybrid nanoparticles (HNPs). Using X-ray scattering, Cryo-electron, and polarized microscopy we show that phosphatidylcholine (PC) and PBD-<i>b</i>-PEO (poly(butadiene-<i>block</i>-ethylene oxide)) hybrid membranes can be nanomanufactured by microfluidics into HNPs with dense and multilayered cores which are ideal carriers of low-solubility drugs of the Biopharmaceutical Classification System (BCS) II and IV such as antimalarial DSM265 and Paclitaxel, respectively.