Biomedical Engineering Reference
In-Depth Information
surface promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity
of cisplatin [196].
The modifi cation of the micelles surface with biofunctional ligands or antibodies is consid-
ered as an effective approach that strengthens the targeting of the micelles into the tumor site and
penetrates the membrane of cancer cells. Nasongkla et al. developed a RGD-functionalized DOX-
loading PEG-PCL micelle. They at fi rst prepared a micelle of PEG-PCL-containing PTX. At the
surface of the micelle, reactive maleimide groups were connected to the PEG molecule chain end.
Then, the cell-recognized peptide RGD was encapsulated on the surface. The dynamic diameter of
the micelles increased from 20.9 nm for the RGD-free micelle to 24.4 nm for the RGD-conjugated
micelles. The internalization of the RGD-functionalized micelles was found to be greatly enhanced.
The cell uptake of the RGD-functionalized micelle increased 30-fold compared with the RGD-free
micelle [197].
It is known that folate receptor overexpressed in some tumor cell membranes. Thus, folate-
conjugated micelles were expected to have specifi c interaction with the tumor cell. Park et al.
reported that amphiphilic block copolymers composed of MPEG and PCL with the folic acid con-
jugated at the surface to produce a folate-receptor-targeted drug carrier for tumor-specifi c drug
delivery. PTX was encapsulated into the micelle in the size range of about 50-130 nm. PTX-loaded
folate-conjugated MPEG/PCL micelles exhibited much higher cytotoxicity for cancer cells than
micelles without the folate group. The folate-functionalized PTX-loaded micelles were receptor-
mediated endocytosed into cancer cells through the interaction with overexpressed folate receptors
on the surface of the cancer cells [198].
Amphiphilic block copolymers based on amorphous polyesters are also be used for the
delivery of other drugs and bioactive molecules. An injectable formulation of rapamycin was
prepared using amphiphilic block copolymer micelles of PEO-PCL with less than 100 nm in
diameter and contained rapamycin at 7% to 10% weight (
1 mg/mL) [199]. PEG-PCL was also
investigated as a drug delivery vehicle for dihydrotestosterone (DHT). The micelles were found
to have a high-loading capacity for DHT, and the release profi le of the drug from the micelle
solution was found to be a slow steady release, which continued over a 1-month period. The
biological activity of the micelle-incorporated DHT was found to be fully retained [200]. PEG-
PCL micelles with encapsulated fenofi brate were prepared for the purpose of control release. The
size of the fenofi brate-loaded PEG-PCL micelles is less than 50 nm, and can encapsulate up to
more than 90% of the initial loading level of fenofi brate at a polymer concentration of 1.0 mg/ml
[201]. Indomethacin-loaded polymeric nanospheres with an average diameter in the range of
less than 200 nm were prepared from amphiphilic PEG-PGA diblock copolymers with different
molar compositions. Indomethacin continuously released from the nanospheres without any burst
effect. Compared with unloaded free drug, these PEG-PG copolymer nanospheres could remark-
ably reduce cell damage [202].
A highly stable polymer micelles, core-surface-cross-linked nanoparticles (SCNPs) made
from amphiphilic poly(ε-caprolactone)-
b
-PEG brush copolymers, were reported to be able to carry
cisplatin, an anticancer drug with low solubility in water. Cisplatin was loaded in the SCNPs with
high-loading effi ciency (approximately 90%).
In vitro
experiments gave out the result that SCNPs
containing cisplatin could be easily taken up by ovarian cancer cells. Much enhanced cytotoxicity
of the cisplatin encapsulated in the SCNPs, compared with free cisplatin, was observed for the
cancer cells. A surface positive charged SCNPs, derived from PCL and (PDMA), was found to have
higher uptake in tumor cells, probably due to the surface positive charge that promoted the cellular
internalization of the nanoparticles, thus resulting in higher cytotoxicity of cisplatin [196].
>
10.4.4 B
LOCK
C
OPOLYMERS
B
ASED
ON
P
OLY
L
-A
MINO
A
CID
(PLAA)
Micelles self-assembled from block copolymers of poly(l-amino acid) (PLAA) and water-soluble
polymer blocks have some unique advantages and are used for drug delivery for specifi c purposes
