Promoting Antitumor Activities of Hydroxycamptothecin by Encapsulation into Acid-labile
Nanoparticles using Electrospraying
Xiaoming Luo,a,1 Guoqing Jia,a,1 Haixing Song,b Chaoyu Liu,a Guannan Wu,a Xiaohong Lia,*
a
Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of
Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China
b Department
1
of Biomedical Science, Chengdu Medical College, Chengdu 610083, P. R. China
These authors contributed equally to the work.
* To whom correspondence should be addressed. (tel.: +8628-87634068; fax: +8628-87634649; e-mail
address: xhli@swjtu.edu.cn)
Running head: Acid-labile nanoparticles for cancer treatment
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Supplementary Material
Electrospraying has been experimentally demonstrated as a viable process for generating micro- or
nanometer particles. Enayati et al. and Jaworek provided details on the background of the
electrospraying process and the effect of process parameters on the characteristics of electrosprayed
nanoparticles (1, 2). In the current study, a grounded copper foil immersed in water and ethanol (1/1,
v/v) was used to collect electrosprayed nanoparticles instead of the commonly used steel plate or
aluminum-foil. Therefore, to quantitatively evaluate and statistically analyze the effects of solution
properties and processing parameters on the nanoparticle properties, an orthogonal experimental design
was applied (3). The concentration and flow velocity of polymer solution, and the nozzle size were
selected as the test factors, and three levels were set for each factor. The concentrations of polymer
solutions were set at 3.0%, 5.0% and 7.0%, the flow velocities were 2.0, 3.0 and 4.0 ml/h, and the
nozzle sizes were 0.45, 0.55 and 0.60 mm. The orthogonal table L9(3)4 was designed, in which a blank
column was designated for error evaluation. The electrospraying process was set up as mentioned in the
main text, and the particle size was measured by a Nano-ZS laser particle analyzer (Zetasizer Nano ZS,
Malvern Co., UK). Table S1 summarizes the orthogonal table and the sizes of electrosprayed
nanoparticles.
A range analysis was aimed to clarify the significance levels of different factors that may have effects
on the nanoparticle size. Those most significant factors could also be disclosed basing on the results of
range analysis. Table S1 summarizes the statistics analysis of the effect of different factors on the
diameters of electrosprayed nanoparticles. The K value for each level of a parameter was the average of
six values shown in Table S1, and the range value (R) for each factor was the difference between the
maximal and minimal values of three levels. As shown in Table S1, the significance sequence of all the
investigated factors was lined as follows: polymer concentration, nozzle size, and flow rate.
Statistics software of SPSS 12.0 was used for the regressive analysis. The polymer concentration (X1,
%) and nozzle size (X2, mm) were set as variables, and the dependent variable was the nanoparticle size
(Y, nm). The linear dependence regression equation was:
Y=113.0+14.92X1+95.2X2
(R2=0.931)
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The correlation coefficients of the regression analysis were relatively high, which was in agreement
with the requirements of statistic analysis. It was suggested that the solution concentration and nozzle
size had regular effects on the nanoparticle size.
Table S1. Design of orthogonal Table L9(3)4 and the sizes of electrosprayed nanoparticles.
Polymer conc.
Flow rate
Nozzle size
Size
(%)
(ml/h)
(mm)
(nm)
1
3.0
2.0
0.45
201
2
3.0
3.0
0.55
217
3
3.0
4.0
0.60
221
4
5.0
3.0
0.60
263
5
5.0
4.0
0.45
243
6
5.0
2.0
0.55
250
7
7.0
4.0
0.55
275
8
7.0
2.0
0.60
273
9
7.0
3.0
0.45
270
K1
213.0
241.3
238.0
K2
252.0
250.0
247.3
K3
272.7
246.3
252.3
R
59.7
8.67
14.3
Exp. No.
To validate the results of the regression analysis, several batches of drug-loaded nanoparticles were
prepared to clarify the differences between the predicted and experimental values. Table S2 summarizes
the results, indicating a good agreement of the observed values with the predicted ones. When the
regression equation was set up for the electrospraying system, nanoparticles with a certain range of
diameter can be obtained through designing the process parameters. Thus, the optimization of process
parameters would be greatly simplified, which was essential for the scale-up of electrospraying system
to meet wide applications.
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Table S2. Validation tests of the orthogonal experimental analysis
Polymer Conc.
Nozzle size
Flow rate
(%)
(mm)
(ml/h)
Batch No.
Average size (nm)
Cal.
Exp.
1
2.0
0.45
3.0
193
213
2
5.0
0.55
2.0
255
268
3
7.0
0.55
4.0
287
272
4
10.0
0.45
4.0
323
356
5
3.0
0.55
3.0
233
252
References
1.
Enayati M, Chang MW, Bragman F, Edirisinghe M, Stride E. Electrohydrodynamic preparation of
particles, capsules and bubbles for biomedical engineering applications. Colloids Surf A.
2011;382:15464.
2.
Jaworek A. Micro- and nanoparticle production by electrospraying. Powder Technol.
2007;176:1835.
3.
Cui WG, Li XH, Zhou SB, Weng J. Investigation on process parameters of electrospinning system
through orthogonal experimental design. J Appl Polym Sci. 2007;103:310512.
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