Supporting Information
DPPC/poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline)
chimeric
nanostructures as potential drug nanocarriers
Natassa Pippa 1,2, Eleni Kaditi 2, Stergios Pispas2,§, Costas Demetzos1,§,*
1
Department of Pharmaceutical Technology, Faculty of Pharmacy, National and
Kapodistrian University of Athens, Panepistimioupolis Zografou 15771, Athens,
Greece
2
Theoretical and Physical Chemistry Institute, National Hellenic Research
Foundation, 48 Vassileos Constantinou Avenue, 11635, Athens, Greece
(*) Corresponding author. Tel.:+30 2107274596; fax: +30 2107274027; E-mail
address: demetzos@pharm.uoa.gr (Prof. C. Demetzos)
§ These
authors contributed equally to this work.
1
IND Incorporation Efficiency
IND concentration was estimated with the aid of the following IND calibration curve
in chloroform:
IND concentration (
absorbance + 0.0567
mg
(R2 = 0.9985)(𝐒𝟏)
⁄ml) =
0.0667
Preparation of MPOx and MPOx:IND nanostructures
Briefly, appropriate amounts of MPOx and MPOx:IND (9:1 molar ratio) were
dissolved in chloroform/methanol (9:1 v/v) and then transferred into a round flask
connected to a rotary evaporator (Rotavapor R-114, Buchi, Switzerland). Vacuum
was applied and a thin film of the materials was formed by slow removal of the
solvent at 50°C. The film was maintained under vacuum for at least 24h in a
desiccator to remove traces of solvent and subsequently it was hydrated in Phosphate
Buffer Saline (PBS), by slowly stirring for 1h in a water bath at 45°C. The resulting
suspensions were subjected to two, 3min and 2min sonication cycles (amplitude 70,
cycle 0.7) interrupted by a 3min resting period, in a water bath, using a probe
sonicator (UP 200S, dr. Hielsher GmbH, Berlin, Germany). The solutions were
allowed to anneal for 30min. The mean hydrodynamic radius, Rh, was used for the
characterization of the nanoassemblies immediately after preparation (t = 0d), as well
as the fractal dimension (df) and the ζ- potential.
The mean hydrodynamic radius of empty MPOx nanocontainers was found Rh=40nm
and the population of nanoparticles is quite polydisperse (PD.I.=0.51). The ζ-potential
values of MPOx nanoassemblies in PBS were found near zero (+2.1 mV), because of
the absence of net charges on nanostructure surface. The fractal dimension (df) was
found near to 2.50 and the ratio Rg/Rh was found equal to 0.81, indicating spherical
2
particles. On the other hand, the incorporation of indomethacin led to a decrease in the
size of MPOx nanocarriers, because the hydrodynamic radius of MPOx:IND
nanoparticles was found equal to 22 nm. This can be attributed to the partial
amphiphilic character of IND due to the presence of –COOH group. The polymeric
nanoparticles containing IND had also lower polydispersity (PD.I.=0.33). The drug
incorporation efficiency was estimated to 30%.
3
Rh distributions for DPPC:MPOx chimeric nanoassemblies in PBS
(a)
1,0
0,8
f(Rh)
0,6
0,4
0,2
0,0
1
10
100
1000
10000
100000
Rh(nm)
(b)
1,0
0,8
f(Rh)
0,6
0,4
0,2
0,0
1
10
100
1000
10000
Rh(nm)
Fig. S1. Distributions of hydrodynamic radius for DPPC:MPOx (a) 9:0.5 and (b) 9:3
molar ratio) nanoassemblies in PBS at 25ºC, at a scattering angle θ=90º and at
concentration c=5x10-3 mg/mL. Distributions of Rh were obtained by the CONTIN
software and seem to be asymmetric with a tail at higher sizes.
4
Rh distributions for DPPC:MPOx (9:3 molar ratio) chimeric nanocarriers in biological
medium
1,2
(a)
1,0
f (Rh)
0,8
0,6
0,4
0,2
0,0
1
10
100
1000
10000
Rh (nm)
1,2
(b)
1,0
f(Rh)
0,8
0,6
0,4
0,2
0,0
1
10
100
1000
10000
Rh(nm)
(c)
1,0
0,8
f (Rh)
0,6
0,4
0,2
0,0
1
10
100
1000
10000
Rh (nm)
5
Fig. S2. Distributions of hydrodynamic radius (a) of FBS components and for
DPPC:MPOx (9:3 molar ratio) nanoassemblies in (b) FBS and in (c) PBS-FBS 10%.
at a scattering angle θ=90º and a concentration c=5x10-3 mg/mL. Distributions of Rh
were analyzed by the CONTIN software.
6