Mass Production and Size Control of Lipid–Polymer Hybrid Nanoparticles through Controlled Microvortices

Lipid–polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process but are restricted by a low throughput. In this study, we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e., Reynolds number (30–150)) we can control the nanoparticle size (30–170 nm) with high productivity (∼3 g/hour) and low polydispersity (∼0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery

Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly­(lactic-<i>co</i>-glycolic) acid (PLGA) polymer is formulated into a polymer–lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging

Single Step Reconstitution of Multifunctional High-Density Lipoprotein-Derived Nanomaterials Using Microfluidics

High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted delivery of therapeutic and diagnostic agents. The current methods for HDL reconstitution involve lengthy procedures that are challenging to scale up. A central need in the synthesis of rHDL, and multifunctional nanomaterials in general, is to establish large-scale production of reproducible and homogeneous batches in a simple and efficient fashion. Here, we present a large-scale microfluidics-based manufacturing method for single-step synthesis of HDL-mimicking nanomaterials (μHDL). μHDL is shown to have the same properties (<i>e.g.</i>, size, morphology, bioactivity) as conventionally reconstituted HDL and native HDL. In addition, we were able to incorporate simvastatin (a hydrophobic drug) into μHDL, as well as gold, iron oxide, quantum dot nanocrystals or fluorophores to enable its detection by computed tomography (CT), magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our approach may contribute to effective development and optimization of lipoprotein-based nanomaterials for medical imaging and drug delivery