Microfluidic synthesis of rigid nanovesicles for hydrophilic reagents delivery.
Bottom Line: The formation mechanism of the RNV is investigated by dissipative particle dynamics (DPD) simulations.The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside the hollow water core of RNV is ≈90 %.In comparison with the combination of free Dox and siRNA, RNV that co-encapsulate siRNA and doxorubicin (Dox) reveals a significantly enhanced anti-tumor effect for a multi-drug resistant tumor model.
Affiliation: Beijing Engineering Research Center for BioNanotechnology & CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, No.11 ZhongGuanCun BeiYiTiao, Beijing, 100190 (P. R. China).Show MeSH
Related in: MedlinePlus
Mentions: Here we report on a multi-stage microfluidic chip to manufacture water core/PLGA shell/lipid layer rigid nanovesicles (RNVs) to entrap varying hydrophilic reagents into the water core regardless of their properties such as molecular weight, surface charge, and so forth. We refer to this nanocarrier as rigid nanovesicle because compared to lipid/cell membrane-like vesicles with Young’s modulus of ≈1 MPa, the PLGA shell in RNV results in a much stiffer structure with Young’s modulus of ≈1 GPa.[4a] The microfluidic chip consists of three stages: 1) The first stage has three inlets and a straight channel (two side inlets for introducing PLGA and 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) in N,N-dimethylformamide (DMF), and one center inlet for hydrophilic reagents such as siRNA, calcein and rhodamine B in water). 2) The second stage has two side inlets for water sheaths and one straight channel. 3) The third stage has one center inlet for DPPC, DSPE-PEG, and cholesterol in ethanol and a spiral channel (Scheme 1 and Figure S1 in the Supporting Information). In this work, the flow rate ratio (FR) of side inlets to middle inlet at different stages is optimized for synthesis of RNV, and the production rate of RNV is 114 µg min−1 by the microfluidic chip (Supporting Information). The transmission electron microscopy (TEM) image of an assembled RNV collected from the outlet shows a hollow core–shell structure with a bright water core and an intact PLGA shell (Figure 1 A). We use the positively charged DOTAP to form the reverse micelle as well as the inner surface of PLGA shell because DOTAP can interact with the negatively charged siRNA, thus ensuring an efficient encapsulation of siRNA inside the water core. Meanwhile, the lipids (DPPC, DSPE-PEG, and cholesterol) are assembled onto the outer surface of PLGA shell in the third stage of microfluidic chip, in order to achieve a long-term stabilization and a long circulation time.
Affiliation: Beijing Engineering Research Center for BioNanotechnology & CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, No.11 ZhongGuanCun BeiYiTiao, Beijing, 100190 (P. R. China).