صفحه 1:
Nanographene oxide as a switch for CW/pulsed NIR laser triggered drug
release from liposomes
صفحه 2:
Lippsowes
* Liposomes have a long history as drug delivery vehicles
and some liposomal formulations have been approved for
clinical applications or currently are undergoing clinical
trials
* Thermosensitive liposomes which are prepared with lipids
having a higher phase transition temperature (transition
from ordered gel phase to liquid-crystalline state) than
physiological temperature (37 °C) can release their cargo
in response to a mild hyperthermia
صفحه 3:
یر
+ The light-triggered release is particularly attractive because it
can be applied noninvasively with precise spatial and temporal
control
* near infrared (NIR) light has gained increasing interest because
of its relatively high tissue penetration and non-toxicity
Near IR CW laser is mainly used for photothermal therapy of
tumor tissues, but can also be used for on-demand drug release
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صفحه 4:
Gropkeve oxide
* Graphene oxide (GO) is a unique two-dimensional (2D)
nanomaterial with interesting physiochemical properties.
٠ GO also possesses a high photothermal effiffifficiency in
response to NIR light, useful for photothermal ablation of
tumor tissues
* Therefore, GO can be an effffective candidate for NIR light-
driven release from liposomes.
صفحه 5:
Wistory
Previous studies of GO and liposomes have mainly focused on the
adsorption of small liposomes (< 200 nm) on large (> 1 pm) GO sheets
and their interaction In contrast, no study has ever reported the
integration of nanosized (< 100 nm) GO into the liposome.
In this study, our objective was to apply nanosized GO (nGO) sheets as
an NIR light controlled switch for the controlled on demand release
from liposomes.
To demonstrate that, we have integrated small size nGO sheets (~40
nm) into larger size (> 800 nm) liposomes and compared the in vitro
release by NIR light. 5 / .
صفحه 6:
ححعلمس6)
* DPPC (5 mg) dissolved in chloroform (1 ml) was taken in a glass tube.
+ The lipid film was prepared by slowly evaporating the solvent under a
steady flow of nitrogen gas and the tube was kept in vacuum for 24 h to
remove any residual solvent.
+ Then, the dry lipid film was hydrated with nGO solution (200 pg/ml) at
50 °C with gentle swirling and extruded through an 800 nm
polycarbonate membrane using a mini-extruder system to obtain nGO
containing DPPC liposomes (nGO-liposome).
+ After extrusion, the nGO-liposomes were separated from free nGO by
centrifugation at 5000 rpm for 10 min at 4 °C. sty 1 0
صفحه 7:
&
|
8
٠ ۲۳6 2۷6۲296 526 0۲ ۱60۵ ۷۵5 -0
nm, as measured by DLS
‘erent ny (8)
+ 4g of nGO was integrated into 1 mg
of lipid, as calculated from the
absorbance measurement ee
b) 1010
+ The average size of the blank 5
liposomes and nGO containing s™
liposomes were 890 + 65 nm and 920 5m
+ 75 nm, respectively 200
صفحه 8:
nGO showed a highly negative surface charge وج
)-47.5 + 3.5 mV) due to the presence of ۱ سقس
carboxyl (COOH) groups. 6 ص
implying that nGO was not present on the
surface of the liposomes.
the nGO incorporation into the liposome was not
due to the simple adsorption of nGO onto the
liposome surface.
:
é
4
0
Therefore, the nGOs must be integrated into the
liposomes, either in the aqueous core or in the
bilayer
صفحه 9:
However, unfortunately, the low contrast of a) 3 ۳
nGO under TEM and their small size (~40
nm) made it impossible to directly visualize
the nGOs in the liposome.
صفحه 10:
a selected area electron diffraction (SAED)
analysis of the liposomes showed the clear
diffraction spots a characteristic of crystalline
structure often found in the graphene oxide
monolayer
The relative intensity profile of the diffraction
spots matched perfectly with that of a graphene
oxide, confirming the presence of nGO in the
liposomes
صفحه 11:
Quenching of fluorescently labeled (NBD-PC)
liposomes by integration of nGO into liposomes. d)
pidesesstios’
8 8
. 8 mm
InialnGO Concertino)
صفحه 12:
20
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ومسمرعريده بردمو (96)
صفحه 13:
a)
Temperature‘)
Laser irradiation time (min)
2 min min 10 min
Boo
wie
صفحه 14:
Two plausible mechanisms of drug release from nGO-liposomes in
response to NIR laser might be suggested.
Firstly, hyperthermia caused by the photothermal property of nGO
may lead to the temperature increase of the lipid bilayer of the
liposome above the melting temperature of the lipid, making the
liposomes leaky.
Secondly, the formation of transient pores in the lipid bilayer by
microbubble cavitation during laser irradiation can also allow the
release of encapsulated compound.
صفحه 15:
In the case of CW laser irradiation, the solution temperature reached
to ~45 °C, higher than the phase transition temperature (Tm ~41.8
°C) of DPPC.
Thus, it was obvious that the temperature of liposome bilayer was
above the melting temperature of DPPC, making the liposomes
permeable and allowing easy release of the encapsulated calcein
Qe