## 2 Materials and Methods
### Empirical Factors and Orthogonal Design  
We selected six factors for analysis, including PLGA concentration in the solution, volumetric flow rate of the solution, travel distance between the needle tip and the ground collection disk, positive voltage applied to polymer solutions, size of the needle, and type of solvent used. The concentration of PLGA in the solution was 3, 5, or 7% (_w/v_). The flow rate of the solution was 0.6, 0.8, or 1.0 mL/h. The travel distance was set at 10, 13, or 15 cm. The voltage was maintained at 11, 14, or 17 kV. The diameter of the needles included, 0.64 mm (20G), 0.51 mm (22G), and 0.40 mm (24G). Meanwhile, three types of solvents were employed, namely hexafluoro-2-propanol (HFIP), dichloromethane (DCM), and trichloromethane (TCM). Table 1 shows the selected factors and factor levels.  
After electrospray, the morphology of electrosprayed particles was inspected under a field emission scanning electron microscope (FESEM; JEOL Model JSM-7500F, Tokyo, Japan). The particle sizes were determined by manually evaluating SEM photos of 30 randomly selected particles for each test run (n = 3). We adopted the L18 orthogonal array design (Table 2) for analysis. The array stipulates the way of conducting the minimal number of experiments, which could provide the full information of all the factors that influence the performance parameter [17]. Since the electrospraying of tiny-sized particles is desired in this study, the optimum processing condition could be acquired by integrating all the factor levels that possess the smallest particle sizes.  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Factors** & **Level 1** & **Level 2** & **Level 3** \\ \hline A: Polymer concentration (\%, _w/v_) & 3 & 5 & 7 \\ B: Flow rate (mL/h) & 0.6 & 0.8 & 1.0 \\ C: Travel distance (cm) & 10 & 13 & 15 \\ D: Voltage (kV) & 11 & 14 & 17 \\ E: Size of needle (mm) & 0.64 & 0.51 & 0.40 \\ F: Solvent & DCM & HFIP & TCM \\ \hline \hline DCM: Dichloromethane; HFIP: Hexafluoro-2-propanol; TCM: Trichloromethane. \\ \hline \end{tabular}
\end{table}
Table 1: Factors and factor levels selected in the main experiment.  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Run** & \begin{tabular}{c} **A: Polymer** \\ **Concentration (\%, _w/v_)** \\ \end{tabular} & \begin{tabular}{c} **B: Flow rate** \\ **(mL/h)** \\ \end{tabular} & \begin{tabular}{c} **C: Travel** \\ **Distance (cm)** \\ \end{tabular} & \begin{tabular}{c} **D: Voltage** \\ **(kV)** \\ \end{tabular} & \
\begin{tabular}{c} **E: Size of** \\ **Needle (mm)** \\ \end{tabular} &
\begin{tabular}{c} **F: Solvent** \\ \end{tabular} \\ \hline
1 & 3\% & 0.6 & 10 & 11 & 0.64 & DCM \\
2 & 3\% & 0.8 & 13 & 14 & 0.51 & HFIP \\
3 & 3\% & 1 & 15 & 17 & 0.40 & TCM \\
4 & 5\% & 0.6 & 10 & 14 & 0.51 & TCM \\
5 & 5\% & 0.8 & 13 & 17 & 0.40 & DCM \\
6 & 5\% & 1 & 15 & 11 & 0.64 & HFIP \\
7 & 7\% & 0.6 & 13 & 11 & 0.40 & HFIP \\
8 & 7\% & 0.8 & 15 & 14 & 0.64 & TCM \\
9 & 7\% & 1 & 10 & 17 & 0.51 & DCM \\
10 & 3\% & 0.6 & 15 & 17 & 0.51 & HFIP \\
11 & 3\% & 0.8 & 10 & 11 & 0.40 & TCM \\
12 & 3\% & 1 & 13 & 14 & 0.64 & DCM \\
13 & 5\% & 0.6 & 13 & 17 & 0.64 & TCM \\
14 & 5\% & 0.8 & 15 & 11 & 0.51 & DCM \\
15 & 5\% & 1 & 10 & 14 & 0.40 & HFIP \\
16 & 7\% & 0.6 & 15 & 14 & 0.40 & DCM \\
17 & 7\% & 0.8 & 10 & 17 & 0.64 & HFIP \\
18 & 7\% & 1 & 13 & 11 & 0.51 & TCM \\ \hline \hline \end{tabular}
\end{table}
Table 2: L’18 (36) orthogonal array used in the main experiment.