Microfluidic Assisted Nanoprecipitation of PLGA Nanoparticles for Curcumin Delivery to Leukemia Jurkat Cells

Abstract

The ability to control particle size and size distribution of nanoparticles for drug delivery is essential because it impacts on the biodistribution and cellular uptake of nanoparticles. We present a novel microfluidic assisted nanoprecipitation strategy that enables synthesis of surfactant-free curcumin encapsulated poly(lactide- co-glycolide) nanoparticles (Cur-PLGA NP) with adjustable particle diameters (30-70 nm) and narrow particle size distribution (polydispersity index less than 0.2). Our Cur-PLGA NP exhibit excellent colloidal stability and inhibit degradation of curcumin. We further demonstrate the potential of our Cur-PLGA NP as a nanotoxic delivery system for curcumin. Cellular viability assay validates a dose-dependent cytotoxicity of Cur-PLGA NP in leukemia Jurkat cells. In contrast, Cur-PLGA NP does not alter the viability of fibroblast NIH3T3 cells, which suggests that the cytotoxicity of Cur-PLGA NP is specific to cell types. Furthermore, there is no detectable effect by PLGA NP to both leukemia Jurkat cells and fibroblast NIH3T3 cells, highlighting the nontoxic nature of our delivery system. Confocal cell uptake studies indicate that PLGA NP do not alter the cell uptake of curcumin. Our microfluidic assisted approach offers a controlled and effective nanobiomaterials synthesis of drug delivery system for curcumin, which can be extended to different capsule materials for a variety of biomedical applications.

Microfluidics for producing polylactide nanoparticles and microparticles and their drug delivery application

“…This result indicates that cumarin incubated in NPs is stabilized by the PLGA shell and protected against rapid degradation; therefore it exhibits high anti‐cancer activity. The experiments demonstrate that PLGA‐cumarin NPs and native cumarin are non‐toxic to NIH3T3 cells but in the case of leukaemia Jurkata cells viability of the cellular line strongly depends on the concentration of cumarin in the NPs …”

Synthesis of Polycaprolactone Nanoparticles through Flow‐Focusing Microfluidic‐Assisted Nanoprecipitation

“…Despite the simple strategy of NP production by batch methods, they usually suffer from nonuniform mixing of fluids [13] and polymer NPs with large sizes and high polydispersity index (PDI) [15][16][17]. An extensive effort is required to manufacture degradable polymer particles with defined sizes through suitable control of their production process, optimization of the mixing conditions, and increased mass transfer between the two phases [18,19]. Previous studies demonstrated that these conditions are provided by applying microfluidic devices, which improve the control of the size and size distribution of particles [17,[20][21][22].…”

“…The mixing performance of microfluidic devices strongly depends on their geometry, e.g., mixing channel and mixing junction, and operational parameters in micro-fluidic-assisted nanoprecipitation. The microfluidic hydrodynamic flow-focusing (MHFF) device integrates controlled mixing with a nanoprecipitation process for synthesizing polymer NPs and drug encapsulation [18,19,25].…”

“…In this device, two aqueous streams with relatively high flow rates enclose an organic stream, and rapid mixing is provided through diffusion mass transfer to produce monodisperse polymer NPs with adjustable characteristics such as drug encapsulation efficiency and controlled rate of release. The controlled regime of the mixing can be precisely tuned by changing the flow rate ratio (FRR) of the aqueous to organic streams and total flow rate (TFR) of both the streams as operational parameters [18,19].…”

Cavitation-Assisted Micromixing for Polymeric Nanoparticle Generation

“…A promising method to achieve this is microfluidics-assisted nanoprecipitation, namely the generation of PNPs based on mixing of parallel streams of a polymer-solution and a miscible non-solvent in a microfluidic channel [3]. In these processes, easily controlled experimental parameters such as flow rates, flow rate ratios or solution composition allow tuning the size and composition of the generated PNPs [3,4]. In this case, though, several process parameters (e.g., the size distribution) strongly depend on how rapidly and uniformly the two fluids are mixed.…”