Fig 1.
Experimental CES system for fabricating drug-loaded MPs.
(a) Schematic of the CES setup including a droplet generation module (twin syringe pump, coaxial needle, electrodes with high voltage power supplies and ground), a droplet collection module (collector with magnetic stir bar), and a process monitoring module (light source, microscopic lens combined with CCD camera and computer); (b) Pictures of the inner needle, the outer needle and the assembly of the coaxial needle.
Fig 2.
Four sequential flow modes of CES with the increased positive voltage.
(a) Dripping mode, V1 = 1.5 kV; (b) Coning mode, V1 = 3.5 kV; (c) Stable cone-jet mode, V1 = 5 kV; (d) Multi-jet mode, V1 = 7 kV. The applied voltages: V2 = 1.5 kV, V3 = -5 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution, Qout = 1.0 mL/h; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution, Qin = 1.0 mL/h; The vertical distances: h = 0.1 mm, H1 = 2.5 mm, H2 = 20 mm, H3 = 100 mm.
Fig 3.
The stable cone-jet mode and the curcumin-loaded PLGA droplets produced by a CES process.
(a) The morphology of the coaxial cone and the coaxial jet; (b) Microscopic image of curcumin-loaded PLGA droplets directly collected by a glass slide, right after the breakup of the coaxial jet; (c) The size distribution of the collected droplets. The applied voltages: V1 = 4.8 kV, V2 = 1.5 kV, V3 = -8 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution, Qout = 1.0 mL/h; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution, Qin = 1.0 mL/h; The vertical distances: h = 0.2 mm, H1 = 2.5 mm, H2 = 20 mm, H3 = 80 mm.
Fig 4.
The influence of applied positive voltage V1 on the stable coaxial cone-jet mode and the size of resultant droplets.
(a) Sequence of experimental images showing the stable cone-jet structure changing with V1; (b) The angle of the cone θ as a function of V1; (c) The diameter of the resultant droplets Dd as a function of V1. The applied voltages: V2 = 1.5 kV, V3 = -8 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution, Qout = 1.0 mL/h; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution, Qin = 1.0 mL/h; The vertical distances: h = 0.3 mm, H1 = 2 mm, H2 = 20 mm, H3 = 80 mm.
Fig 5.
The influence of outer liquid flow rate Qout on the stable cone-jet mode and the size of resultant droplets.
(a) Sequence of experimental images showing the stable cone-jet structure changing with Qout; (b) The angle of the cone θ as a function of Qout; (c) The diameter of the resultant droplets Dd as a function of Qout. The applied voltages: V1 = 4 kV, V2 = 1.5 kV, V3 = -5 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution, Qin = 0.2 mL/h; The vertical distances: h = 0.3 mm, H1 = 2 mm, H2 = 20 mm, H3 = 80 mm.
Fig 6.
Core-shell structure of curcumin-loaded PLGA droplets produced by CES.
(a) Confocal fluorescence microscopic image of droplets showing the shell shape (Nile red 0.01 w% in outer liquid); (b) Confocal fluorescence microscopic image of MPs showing the core (I), the shell (II) and the core-shell shapes (III) (Nile red 0.01 w% in outer liquid and coumarin-6 0.01 w% in inner liquid). The applied voltages: V1 = 4.8 kV, V2 = 1.5 kV, V3 = -5 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution, Qout = 1.0 mL/h; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution, Qin = 0.5 mL/h; The vertical distances: h = 0.2 mm, H1 = 2 mm, H2 = 20 mm, H3 = 80 mm.
Fig 7.
Mass production of curcumin-loaded PLGA MPs produced by CES.
(a) SEM imaging and (b) size distribution of the MPs for Qout = Qin = 1.0 mL/h; (c) SEM imaging and (d) size distribution of the MPs for Qout = 1.0 mL/h and Qin = 0.5 mL/h. The applied voltages: V1 = 4.8 kV, V2 = 1.5 kV, V3 = -8 kV; The outer liquid: 10.0 w% PLGA (Mw = 10,000) in ethyl acetate solution; The inner liquid: 4.0 w% curcumin and 1.0 w% PLGA (Mw = 50,000) in acetone solution; The vertical distances: h = 0.2 mm, H1 = 2.5 mm, H2 = 20 mm, H3 = 80 mm.
Table 1.
The EE and LR of drugs for curcumin-loaded PLGA MPs fabricated in CES.
The applied voltages: V1 = 4.8 kV, V2 = 1.5 kV, V3 = -8 kV; The outer liquid: PLGA (Mw = 10,000) in ethyl acetate solution; The inner liquid: 4.0 w% curcumin and PLGA (Mw = 50,000) in acetone solution; The vertical distances: h = 0.2 mm, H1 = 2.5 mm, H2 = 20 mm, H3 = 80 mm.
Fig 8.
Comparison of the curcumin release profiles versus time at different conditions.
(a) Picture of four samples and schematics of corresponding structures of free curcumin, ES and CES MPs; (b) Drug release profile in 40 days of free curcumin and MPs prepared by ES and CES; (c) The enlarged figure of the release profile in first 12 hours.