Biomedical Engineering Reference
In-Depth Information
a
Drug-loaded
PEG-PLA
Polymersome
10 nm
DOX ppt.
20 nm
c
b
Saline or Empty
Polymersome
1.0
100
1.0
37 °C
80
pH 5.5
Free Drug
0.8
37
°
C
60
pH 7.4
0.5
01 2 345
Time (days)
0.6
40
Polymersome-loaded
4°C
20
pH 7.4
0.4
0
0
20
40
60
80
1 mo
0
1
2
3
4
5
Polymersome Incubation Time
In Vitro
(hr)
Days After Tail-vein Injection
Fig. 11 Drug loading, release, and antitumor activity of biodegradable polymersomes.
(a) Cryo-TEM image of DXR- and PTX-loaded PEG-
b
-PLA/PEG-
b
-PBD polymersomes.
(b) PEG-
b
-PLA/PEG-
b
-PBD polymersomes visibly porate and release encapsulates in isotonic
PBS, pH 7.4 at 37
C and even faster in isotonic HEPES, pH 5.5 at 37
C, but the polymersomes
are stable in PBS at 4
C. (c) Solid tumors shrink after a single injection of (DXR + PTX)-loaded
polymersomes. Reprinted from [
230
] with permission
disintegration. Cellular uptake studies of the blend polymersomes showed that these
polymersomes were hydrolyzed within the endolysosomal compartments and
released their contents [
230
]. Furthermore, in vivo studies demonstrated growth
arrest and shrinkage of rapidly growing tumors after intravenous injection of
the polymersomes (Fig.
11c
). Combination therapy with DXR- and PTX-loaded
polymersomes triggered apoptosis in the tumors. Apoptosis was enhanced twofold
with polymersome-delivered drug compare with free drug.
In addition to low molecular weight drugs, PEG-
b
-polyester polymersomes
can encapsulate water-soluble macromolecular drugs, e.g. proteins and nucleic
acids, into the hydrophilic interior space. Indeed, PEG-
b
-PLA and PEG-
b
-PCL
polymersomes have been reported as potential oxygen nanocarriers by Palmer
and coworkers [
231
]. Hemoglobin-loading efficiencies of up to 20% were obtained
for polymersomes prepared from PEG-
b
-PLA and PEG-
b
-PCL copolymers with
shorter hydrophobic polyester blocks. Furthermore, oxygen affinity, cooperativity
coefficient, and methemoglobin level of the polymersomes were consistent with
values required for efficient oxygen delivery in the systemic circulation. Discher
and coworkers have demonstrated loading and functional delivery of siRNA with
polymersomes of nonionic PEG-
b
-PLA copolymers [
232
]. The biodegradable
polymersomes are taken up passively by cultured cells, after which the vesicles
transform into micelles that allow endolysosomal escape and delivery of siRNA
