Biomedical Engineering Reference
In-Depth Information
and ability to encapsulate or integrate a broad range of drugs. h e rela-
tively long blood circulation times can be achieved by the introduction
of a hydrophilic nonfouling surface layer (e.g., PEG) [57]. Additionally,
diverse functionalities and stimuli-responsiveness can be incorporated
into the structures of vesicles to fabricate the intelligent platforms for
controlled delivery of bioactive agents, particularly antitumor drugs [58].
Of these, the vesicles based on stimuli-responsive polypeptides (e.g., pH-
responsive ones) have been developed as emerging systems for antitumor
drug delivery.
Recently, the pH-responsive vesicle from poly(trimethylene
carbonate)-
block
-P(L-glutamic acid) (PTMC-
b
-PLGA) was developed by
Lecommandoux and coworkers for smart DOX delivery (Figure 15.3A, B
and C). h e vesicle was comprised of a PTMC interlayer as well as outer
and inner PLGA shells, and was prepared by either a direct dissolution
or solvent displacement (nanoprecipitation) method [52]. An ionizable
antitumor drug (i.e., DOX) was encapsulated into the PTMC-
b
-PLGA
vesicle at a pH of either 7.4 or 10.5 [54]. h e distribution of DOX in the
vesicle was signii cantly inl uenced by the loading pH, which can prob-
ably be attributed to the ionization or non-ionization of DOX at pH below
or above its p
K
a
(i.e., 8.25), respectively [3, 60]. When loaded at pH 7.4,
positively charged DOX was partially absorbed in the PLGA shell, whereas
the neutral DOX was encapsulated inside the PTMC layer when loaded
at pH 10.5. As depicted in Figure 15.3D,
in vitro
DOX released from the
drug loaded vesicle was pH and thermo-dependent. An obviously faster
release was observed at pH 5.5 in comparison with that at pH 7.4, which
resulted from the improvement of the hydrophilicity of DOX, and reduc-
tion of electrostatic interaction between PLGA and DOX at pH 5.5 [21,
54]. Furthermore, the faster DOX release was obtained as the temperature
increased from 25 to 45
C, perhaps due to the enhanced permeability and
mobility of the vesicle membrane. Additionally, the above vesicular system
has also been exploited for the codelivery of DOX and superparamagnetic
iron oxide nanoparticle (USPIO, i.e., γ-Fe
2
O
3
) for magneto-chemotherapy
and magnetic resonance (MR) imaging [61, 62].
°
15.2.3 Polypeptide Nanogels
Polymeric nanogels are the swellable nanoscale crosslinked particles that are
prepared through emulsion polymerization, precipitation polymerization,
photolithographic and micromolding techniques, radical heterogeneous
polymerization, supramolecular assembly and shell or core crosslinking
of polymeric micelles, etc. [63-65]. h e nanogels exhibited great prospects
