Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Abstract

Multiphase microfluidics has attracted significant interest in making micro-and nanostructures for various applications because of its capabilities in precisely controlling and manipulating a small volume of liquids. In this review, we introduce the recent advances in making micro-and nanostructures for pharmaceutical applications, including microparticles and microcapsules for controlled release, nanoparticles for drug delivery and microgels for 3D cell culture. With the development of more advanced microfluidic systems, the research focus in this field has shifted from making simple micro-and nanostructures to multifunctional systems to achieve more desirable functions. However, these multifunctions may lose their advantages that have been demonstrated in vitro once they are applied in vivo or later in human. The key challenge is a lack of fundamental understanding of the interactions between the micro-and nanomaterials and the biology systems. Consequently, the translation of these advanced materials lags far behind their extensive laboratory research.To better understand the micro-or nano-bio interactions, the development of new in vivomimicking models is imperative. Microfluidics has demonstrated its great potential in creating physiologically relevant models including 3D cell culture, tumor-on-a-chip and organs-on-a-chip. Therefore, efforts towards developing 3D cell culture and biomimetic chips including tumor-on-a-chip and organs-on-chips for faster and reliable evaluation of these micro-and nanosystems are also highlighted.

Staggered Herringbone Microfluid Device for the Manufacturing of Chitosan/TPP Nanoparticles: Systematic Optimization and Preliminary Biological Evaluation

“…To overcome these issues, several passive continuous flow microfluidics-based approaches have been developed for the NPs synthesis [3,24,25]. Microfluidics-the science and technology of manipulating nanoliter volumes in microscale fluidic channels-has been commonly applied to enhance the rapid and thorough mixing of different fluids (immiscible, partially or mutually soluble), increase mass transfer across phase boundaries, and precisely control physical processes at microscales.…”

“…Microfluidics-the science and technology of manipulating nanoliter volumes in microscale fluidic channels-has been commonly applied to enhance the rapid and thorough mixing of different fluids (immiscible, partially or mutually soluble), increase mass transfer across phase boundaries, and precisely control physical processes at microscales. If fluids contain NPs precursors, the three stages of NPs formation (nucleation, growth through aggregation and stabilization) are well-controlled within microchannels where aggregation can be reduced due to the continuous flow nature of the process [3,25].…”

“…In passive microfluidics techniques for NPs synthesis the proper mixing can be achieved employing special designs of the microfluidic networks and NPs physicochemical features can be tuned by simply adjusting flow rates of the fluids and therefore the mixing time, and formulation parameters such as both fluids characteristics (nature, polarity, density, viscosity, etc.) and composition (NPs precursors types and concentrations) [3,24,25]. Specifically, microfluidics has shown to be an efficient, fully-automated bottom-up technique for the synthesis of NPs with homogeneous and consistent characteristics in terms of size, size distribution, composition and drug release in a well-controlled, reproducible and high-throughput manner; low reagent consumption and short reaction time could further enable screening and optimization of libraries of NPs with customized properties [1].…”

Microfluidic self-assembly of a combinatorial library of single- and dual-ligand liposomes for in vitro and in vivo tumor targeting

“…Microfluidic technology is a newly emerging method for the preparation of various nanoparticles due to its better manipulation of the synthesis process [16][17][18]. To prepare multifunctional liposomes in a single step, a microfluidic hydrodynamic flow focusing (HFF) approach has been developed [19,20]. This method can provide a well-controlled mixing of the organic solvent which contains the lipids and the aqueous buffer in the microfluidic device, thus precisely controlling the properties of the liposomes such as size, charge, and surface chemistry [21].…”

Microfluidic formation of core-shell alginate microparticles for protein encapsulation and controlled release

“…A wide variety of delivery systems have been developed to encapsulate biologic drugs and control their release including polymer particles, inorganic particles, and gel particles [2]. Several polymers such as poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA) have been approved for food and pharmaceutical applications because of their excellent biocompatibility and degradability [3][4][5].…”