Biomedical Engineering Reference
In-Depth Information
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Figure
10.2
Left: Synthesis of PC-grafted polyesters. Right:Ce ltiter-glow
luminescent cell viability assays of polyester-graft-PC after 24 (red)
and 48 hour (blue) incubation in MCF7 cell culture.
the second-stage slow drug release results in low intracellular drug availability,
which is insufficient for killing cancer cells. Conjugation of a drug to an
amphiphilic polymer will overcome these drawbacks. Chen et al.
53
applied
click chemistry to camptothecin (CPT) conjugation on the polyMPC
backbone, using an acylated and azide-modified form of CPT that gives
polyMPC-CPT conjugates with high drug loading, which has potential for
future integration into CPT-based injectable cancer therapeutics. Also the drug
release rates can be controlled by incorporating different linkers between CPT
and the polyMPC backbone (Figure 10.3).
To improve the capability in specific targeting, immobilizable units have to
be introduced into a MPC-containing copolymer to conjugate bio-recognizable
ligands or antibodies. Miyata et al.
54
prepared a PMB polymer with an
immobilizable unit, p-nitrophenylcarbonyloxyethyl methacrylate (NPMA),
which can be modified by the addition of the preS1 domain of hepatitis B
surface antigen (HBsAg) (Figure 10.4). The final NDVs with encapsulated
PTX (PTX/PMBN-preS1) showed human hepatocyte-specific targeting
without serious adverse effects in vivo. The 50% inhibitory concentration
(IC
50
) values of PTX/PMBN-preS1 against the human hepatocellular
carcinoma cell line (HepG2) were lowered to about one-seventh of PTX/
PMBN, the PTX carrier without HBsAg, while the IC
50
values of PTX/
PMBN-preS1 against the human squamous cell carcinoma cell line (A431)
were comparable to that of PTX/PMBN. This result could well provide the
basis for a human hepatocyte-specific drug delivery system in clinical settings.
Shimada et al.
55
also use the same method to conjugate epidermal growth
factor (EGF) on a MPC polymer. The final EGF-PMBN-PTX micelles
represent a more potent targeted therapy for tumors overexpressing EGFR.
Iwasaki et al.
56
synthesized a water-soluble MPC polymer bearing hydrazide
groups functionalized by nonnatural carbohydrates through ketones. The
nanoparticles were able to recognize ManLev-treated HeLa cells. Nonspecific
