Biomedical Engineering Reference
In-Depth Information
3.1.3.2 Relative core microviscosity
As mentioned previously in Stĕpánek's characterization, when the
polymer concentration dependence of the longer PCL block micelles
is absent at low concentration, the micelle is considered to be
kinetically frozen. In this case, the equilibrium will ultimately shift to
form unimers. However the core is so entangled and viscous with the
larger PCL blocks, the time scale of the light scattering experiments
cannot capture this. The relative core microviscosity of micelles can
be estimated based the fluorescent emission intensity ratio of 1,3-
bis-(1-pyrenyl)propane (dipyrene) and pyrene at 480 nm and 390
nm, respectively. Dipyrene forms an excimer when rotation is free
around an alkyl chain between two pyrenes to change conformation
and emits light at 480 nm (
I
E
). The emission of light from pyrene at
390 nm (
I
M
) (in competition with dipyrenes emission at 480 nm) is
used as a reference to the excimer [38]. As the core becomes viscous,
change in conformation is restricted, and the emission intensity at
480 nm decreases, and the ratio
I
M
/
I
E
increases. It should be noted
that the
I
M
/
I
E
or
I
E
/
I
M
ratios are used interchangeably. These types
of characterizations are useful in understanding release profiles
of a model drug among a series of copolymers as well as the
thermodynamic stability of micelles.
3.2
Drug Delivery from Diblock PEO-PCL
Copolymer Micelles
In addition to knowledge of the thermodynamic stability of these
micelles, understanding the thermodynamic affinity of a drug for the
PCL core is also crucial for drug delivery. The impact of core length
on release, biocompatibility, and efficacy
in vitro
in cell culture
has been studied with a variety of lipophilic drugs, especially anti-
cancer agents. Indomethacin, a hydrophobic non-steroidal anti-
inflammatory drug (NSAID) was the first model drug encapsulated
in diblock PEO-PCL micelles [39]. As expected, CMC's decreased with
increasing hydrophobic chain length and were on the order of 10
-7
M (Table 3.1). An encapsulation efficiency of 40% was achieved with
indomethacin in PEO-PCL micelles with block molecular weights of 5
kDa and ~5.5 kDa. Release studies showed indomethacin to release
in a Fickian profile over 12-14 days without a burst eff ect [40].
This work also showed that the micelle size increased when higher
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