Biomedical Engineering Reference
In-Depth Information
understanding will allow researchers to foresee problems with
encapsulation and attack those problems with substituted cores,
additives to increase lipophilicity, or by simply adjusting the core
block length. The synthesis of these micelles, encapsulation, and
release characterizations of anticancer and immunosuppressive
drugs, as well as drug models will be described. The assessment
of the fate of these micelles
in vivo
, cell internalization studies,
pharmacokinetics of drugs and micelles, and tissue distribution
studies will conclude this review.
3.1.1
Synthesis of PEO-Poly(ε-Caprolactone)
PEO-poly(ε-caprolactone) (PCL) is typically synthesized by a
ring-opening polymerization of ε-caprolactone from the terminal
hydroxyl of PEO (Figure 3.1). Ring-opening polymerizations are
generally catalyzed by stannous (II) octoate [16] or hydrochloric acid
[17] but can be non-catalytically polymerized at high temperatures
(160-200
°
C) for several days [18]. Other catalysts such as antimony
compounds suff er from toxicity [19], whereas stannous octoate
is FDA approved as a food additive, and HCl is commonly used in
the formulation of pharmaceutics. The extent of polymerization is
verified through comparison of characteristic peak shift intensities
of PEO (3.39 and 3.64 ppm) and poly(ε-caprolactone) (1.38, 1.65,
2.31, and 4.06 ppm) through H1-NMR in CDCl3 (Figure 3.2).
O
OH
O
O
O
O
n
n
O
Sn(II)Octoate
O
O
O
O
OH
O
OH
O
O
O
n
m
Figure 3.1
Catalyzed polymerization of PCL (m units) with methoxy PEO
(n units).
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