On-chip controlled synthesis of polycaprolactone nanoparticles using continuous-flow microfluidic devices
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On-chip controlled synthesis of polycaprolactone nanoparticles using continuous-flow microfluidic devices Fazlollah Heshmatnezhad 1 & Ali Reza Solaimany Nazar 1 Received: 14 November 2019 / Accepted: 24 March 2020 # Akadémiai Kiadó 2020
Abstract This systematic investigation assessed the potential applications of microfluidic devices in producing a uniform size distribution of polycaprolactone (PCL) nanoparticles by applying the liquid non-solvent precipitation process. Five arrangements of microfluidic devices are fabricated with different designs. The effects of different operational and geometrical factors such as flow rate ratio (FRR), total flow rate (TFR), mixing channel width, mixing channel length, and confluence angles of the inlet channels are investigated on the size, polydispersity index (PDI), and the size distribution of PCL particles. Further, a study was performed to enhance the production throughput of PCL nanoparticles. The mean size of nanoparticles is precisely controlled within the range of 40–370 nm with PDI values of 0.2–0.37. According to the results, the optimal conditions for rapid production of nanoparticles with a size smaller than 200 nm and PDI ≤ 0.31 are obtained at FRR of 8, TFR of 70 ml h−1, channel width of 200 μm, channel length of 20 mm, and the confluence angle of 60o. Furthermore, the microfluidic device with a wider channel width of 600 μm provided a higher productivity rate of the PCL nanoparticles with a similar size and lower PDI than those obtained by other widths. Keywords Microfluidic device . Hydrodynamic focusing flow . Polycaprolactone nanoparticle . Precipitation process
Introduction Biodegradable and biocompatible polymeric nanoparticles (NPs) have attracted considerable attention and are widely recognized as successful drug delivery carriers [1–3]. Among the biodegradable polymers, polycaprolactone (PCL) offers a considerable potential for the controlled drug delivery due to its biocompatibility and biodegradability [4]. The size and size distribution of polymeric NPs are the key parameters that play a significant role in the rate of drug release, drug loading, therapeutic efficacy, drug accumulation on specific sites, and the clearance rate of drug from the body [5, 6]. The size of NPs produced should be controlled as it can affect their therapeutic outcomes, which is dictated by Electronic supplementary material The online version of this article (https://doi.org/10.1007/s41981-020-00092-8) contains supplementary material, which is available to authorized users. * Ali Reza Solaimany Nazar [email protected] 1
Department of Chemical Engineering, University of Isfahan, Isfahan, Iran
production method of carriers [7]. Polymeric NPs are produced via traditional (bulk) methods such as emulsification/ solvent evaporation, salting-out, dialysis, nanoprecipitation, and supercritical fluid technology [8]. Among these methods, the nanoprecipitation is a simple and fast method at ambient conditions without utilizing chemical additives or harsh formulati
