Supporting Information
Smart delivery of flexible azithromycin cationic niosomes for
improved bioavailability and targeting efficiency
The Supplementary Information includes:
Supplementary Figures 1.
Supplementary Tables 1-2.
Supplementary Figure 1. Formulation optimization of AMCNS, i.e., effect of mass ratio of
cholesterol to polysorbate 80, octadecylamine concentration, amount of AM on
incorporation efficiency and drug loading capacity (n=3).
Supplementary Table 1. The changes of size, zeta potential, and encapsulation efficacy
when the AMCNS vesicles were placed at 4℃ for 15 days.
Supplementary Table 2. Mathematical models of mean cumulative release rate versus
time of AMCNS and AM.
Supplementary Table 3. The similarity between the dissolution profiles AMCNS and AM
in different dissolution media.
* These authors (M. Zhong, Y. Feng, H. Liao, X. Hu and S. Wan) contributed equally to this work.
#corresponding author. Medicine Engineering Research Center, Chongqing Medical University,
Chongqing 400016, PR China. Tel.: + 86 13308300303; fax: + 86 23 6848 5161.
E-mail address: zjqrae01@163.com (J. Zhang)
Supplementary Figure 1. Formulation optimization of AMCNS, i.e., effect of mass ratio of cholesterol to polysorbate
80, octadecylamine concentration, amount of AM on incorporation efficiency and drug loading capacity (n=3). The
incorporation efficiencies were determined by reverse dialysis methods.
Supplementary Table 1. The changes of size, zeta potential, and encapsulation efficacy when the AMCNS vesicles
were placed at 4℃ for 15 days. (n=3)
Parameters
AMCNS-S stored in 4℃
AMCNS-L stored in 4℃
0 day
In 15 days
0 day
in 15 days
Size (μm)
(0.95 ± 0.10)
(1.01 ± 0.07)
(5.87 ± 1.80)
(5.90 ± 0.04)
Zeta (mV)
(14.63 ± 0.02)
(13.83 ± 0.05)
(12.51 ± 0.02)
(12.43 ± 0.06)
Encapsulation
(80.46 ± 0.54)
(79.55 ± 0.88)
(92.87 ± 0.77)
(91.70 ± 0.21)
efficacy (%)
Supplementary Table 2. Mathematical models of mean cumulative release rate versus time of AMCNS and AM.
Formulation
Release medium
0.1 mol/L HCl
pH 6.8 PBS
pH 7.4 PBS
AM
Zero-order
Q=1.3448t+63.023,
Q=1.5993t+56.024,
Q=2.1617
r=0.704
r=0.770
r=0.736
ln(1-Q)=-0.0531t-0.389
ln(1-Q)=-0.0563t-0.2905
ln(1-Q)=-0.1449t+0.7773
7, r=0.971
, r=0.980
, r=0.960
kinetic
model
First-order
kinetic
model
Higuchi model
AMCNS-S
Q=10.718t +47.505,
Q=12.557t +38.091,
Q=14.106t1/2+41.124,
r=0.828
r=0.891
r=0.853
(100-Q) =-0.0797t+3.3
(100-Q) =-0.0875t+3.5
(100-Q)1/3=-0.0814t+3.4
model
203, r=0.900
52, r=0.923
258, r=0.899
Ritger-peppas
lnQ=0.1081lnt+1.6862,
lnQ=0.1241lnt+1.6305
lnQ=0.2823lnt+3.8593,
model
r=0.863
r=0.942
r=0.873
Weibull model
lnln[1/1-Q]=0.248lnt-0.5
lnln[1/1-Q]=0.2722lnt-0.
lnln[1/1-Q]=0.5773lnt+0.
404, r=0.965
0.635, r=0.972
4147, r=0.955
Q=1.3035t+70.247,
Q=1.0914t+
r=0.646
r=0.643
r=0.695
ln(1-Q)=-0.0758t-1.262
ln(1-Q)=-0.0684t-0.909,
ln(1-Q)=-0.0695t-0.702,
3 r=0.861
r=0.927
r=0.945
Zero-order
kinetic
First-order
kinetic
model
Higuchi model
1/3
1/2
Hixcon-Crowell
model
AMCNS-L
1/2
t+58.669,
1/2
1/3
58.658,
1/2
Q=1.2519t+51.72,
LnQ=8.7845t +59.014,
Q=10.415t +41.723,
Q=11.584t1/2+33.328,
r=0.773
r=0.797
r=0.835
Hixcon-Crowell
(100-Q)1/3=-0.0625t+3.
(100-Q)1/3=-0.052t+3.3
(100-Q)1/3=-0.0557t+3.
model
0512, r=0.859
944, r=0.836
6183, r=0.874
Ritger-peppas
lnQ=0.1586lnt+4.1387,
lnQ=0.312lnt+3.6622,
lnQ=0.3759lnt+3.4482,
model
r=0.789
r=0.886
r=0.893
Weibull model
lnln[1/1-Q]=0.3451lnt
lnln[1/1-Q]=0.578lnt-0.6
lnln[1/1-Q]=0.641lnt
+0.035, r=0.925
845, r=0.965
-0.9699, r=0.964
Q=0.1435t+77.799,
Q=0.2654t+51.927,
Q=0.2678t+45.69,
r=0.521
r=0.795
r=0.833
ln(1-Q)=-0.0155t-0.494
ln(1-Q)=-0.0141t-0.7315
ln(1-Q)=-0.0112t-0.5727,
3, r=0.948
, r=0.958
r=0.975
Zero-order
kinetic
model
First-order
kinetic
model
Q=0.29399t +68.369,
Q=4.8152t +38.276,
Q=4.7454t1/2+32.607,
r=0.678
r=0.915
r=0.937
Hixcon-Crowell
(100-Q)1/3=-0.0118t+3.
(100-Q)1/3=-0.0115t+3.
(100-Q)1/3=-0.0102t+3.
model
7916, r=0.950
608, r=0.950
7954, r=0.939
Ritger-peppas
lnQ=0.2239lnt+3.421,
lnQ=0.2219lnt+3.4934,
lnQ=0.241lnt+3.3351,
model
r=0.978
r=0.908
r=0.980
Weibull model
lnln[1/1-Q]=0.4066lnt-1.
lnln[1/1-Q]=0.4174lnt-1.
lnln[1/1-Q]=0.401lnt-1.20
1317, r=0.968
0318, r=0.989
09, r=0.991
Higuchi model
Q means cumulative AM release at time t.
1/2
1/2
Supplementary Table 3. The similarity between the dissolution profiles AMCNS and AM in different dissolution
media.
Release profile 1
Release profile 2
Differen
f2
ce
Formulation
Release medium
Formulation
Release medium
AMCNS-S
pH 1.2 HCl solution
AM
pH 1.2 HCl solution
45.11
+
AMCNS-L
pH 1.2 HCl solution
AM
pH 1.2 HCl solution
24.13
+
AMCNS-S
pH 1.2 HCl solution
AMCNS-L
pH 1.2 HCl solution
42.50
+
AMCNS-S
pH 6.8 PBS
AM
pH 6.8 PBS
47.70
+
AMCNS-L
pH 6.8 PBS
AM
pH 6.8 PBS
31.80
+
AMCNS-S
pH 6.8 PBS
AMCNS-L
pH 6.8 PBS
29.59
+
AMCNS-S
pH 7.4 PBS
AM
pH 7.4 PBS
45.37
+
AMCNS-L
pH 7.4 PBS
AM
pH 7.4 PBS
26.90
+
AMCNS-S
pH 7.4 PBS
AMCNS-L
pH 7.4 PBS
30.90
+
AMCNS-S
pH 1.2 HCl solution
AMCNS-S
pH 6.8 PBS
28.39
+
AMCNS-S
pH 1.2 HCl solution
AMCNS-S
pH 7.4 PBS
29.46
+
AMCNS-S
pH 6.8 PBS
AMCNS-S
pH 7.4 PBS
48.66
+
AMCNS-L
pH 1.2 HCl solution
AMCNS-L
pH 6.8 PBS
58.86
-
AMCNS-L
pH 1.2 HCl solution
AMCNS-L
pH 7.4 PBS
67.11
-
AMCNS-L
pH 6.8 PBS
AMCNS-L
pH 7.4 PBS
56.30
-
AM
pH 1.2 HCl solution
AM
pH 6.8 PBS
53.20
-
AM
pH 1.2 HCl solution
AM
pH 7.4 PBS
62.38
-
AM
pH 6.8 PBS
AM
pH 7.4 PBS
68.23
-