Biomedical Engineering Reference
In-Depth Information
as macromolecules with linear arrangements of two or more different blocks of hydrophilic and
lipophilic segments. The self-assembly of these amphiphilic block copolymer to form the core in
aqueous solution is based on the hydrophobic interaction between the lipophilic polymer segments.
The hydrophobic core is sterically stabilized by a hydrophilic palisades formed from the hydro-
philic segments of the block copolymer. The palisades are dense enough to avoid the core from
contacting with the aqueous environment. Thus, the amphiphilic block copolymer micelles are
capable of encapsulating hydrophobic molecules in the core through nonpolar or hydrophobic inter-
action between the lipophilic polymer segments and the hydrophobic drugs. This can increase the
concentration and the stability of hydrophobic drugs in the aqueous environments. The potential
of using amphiphilic block copolymers as colloidal vectors provides the possibility of delivery of
many newly developed highly effi cacious therapeutic compounds that are water-insoluble.
Beyond increasing the solubility of water-insoluble drugs, the amphiphilic block copoly-
mer micelles also act like other kinds of nanodrug carriers, elongating the blood cycling time of
drugs and targeting the payload drug to specifi c tissue or organism through ether passive or active
pathways. In this section, typical amphiphilic block copolymer PEO-PPO-PEO block copolymer
(Pluronic) micelles are discussed, including their composition, structure, preparation, and biomedi-
cal applications as drug carriers.
Pluronics are ABA type tri-block copolymers of polyethylene oxide (PEO) and polypropylene
oxide (PPO) with the PPO segments at the center and PEO segments at both ends of the polymeric
chain. The commercial available Pluronics are generally synthesized from the anionic polymer-
ization ring-opening polymerization of ethylene oxide initiated from the hydroxyl groups at both
ends of PPO chain. Therefore, Pluronics always have controlled molecular architecture and narrow
molecular weight distribution.
Pluronics have been investigated as vectors for drug and gene delivery
in vitro
and
in vivo
and
were demonstrated to have high effi ciency for both the drug and gene transfer
in vivo
[167-170]. The
incorporation of drugs into Pluronic micelles results in increased solubility and stability of drugs. In
addition, the enhanced swallow of the Pluronic micelles by the cell has been well-known [169,171].
Consequently, the micelles are used for delivery of bioactive low-molecular weight compounds in
the body.
Pluronic was used for delivery of ATP into cells. In an intact Jurkat cells culture system, no
participation of the exogenous γ-32P ATP in phosphorylation of intracellular proteins could be
observed, because the negatively charged ATP could not penetrate cell plasma membrane. Whereas
considerable increase of protein phosphorylation was obtained by adding of γ-32P ATP solubilized
in positively charged Pluronic micelles to cells (the positively charged micelles were obtained by
adding of dodecylamine). The Pluronic micelles showed good biocompatibility, not infl uencing the
viability of cells and permeabilize cell plasma membrane under the experimental condition [172].
To target the micelles into the cell, cell targeting ligands can be conjugated with the Pluronic
molecule. The conjugates are incorporated into the micelle by preparing the micelles from the
mixture of Pluronics and the conjugates. The incorporation of ligands capable of receptor-mediated
endocytosis can result in enhancement of the effi ciency of cell loading of the micelles. Using
this concept, the micelles of pluronic P85 incorporated with
Staphylococcus aureus
enterotoxin
B (SEB) ligands were used as microcontainers for
in vitro
delivery of the fl uorescent dye into Jur-
kat and MDCK cells. Enhanced fl uorescence radiation was observed compared with the non-SEB
micelles. At 4°C, under the condition in which endocytosis is abolished, there is no enhancement of
fl uorescence, indicating that the increase of fl uorescence is attributed to the enhanced swallow of
the SEB-incorporated micelles [173].
Pluronic block copolymer micelles are also useful in the delivery of anticancer agents, e.g.,
doxorubicin (DOX), PTX, and platinum compound, into tumor cells [171,174-176]. In the presence
of Pluronic micelles, the obviously increased uptake of these drugs by tumor cells were observed,
apparently due to the effect of the polymeric micelles on cell membrane permeability. One example
of the drug/Pluronic formulation employed PTX as the cytotoxic agent. The spherical PTX-loaded
