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changes in micelle size (using DLS) at different dilutions is
an elegant way to determine micelle stability. Our results
reveal that CM remain intact even below the CMC [Fig. 8(A)]
while NCM disintegrated. CMC for CM was found to be
20-fold lower compared to NCM confirming the fact that CM
were several times more stable than their non-crosslinked
counterparts. It is worth mentioning that, although CMC of
CM has little practical meaning it still provides a reasonable
measure of the extent in improvement in micelle mechanical
integrity. Micelles have also been shown to become unstable
once they encounter blood components.11,36,38 Instability
may result from protein adsorption, protein penetration, or
drug extraction.36 As the most abundant protein in blood
plasma is serum albumin, we investigated the effect of physi-
ological simulating concentrations of BSA (45 mg/mL) on
Cm and NCM stability using DLS to observe time-dependent
changes in micelle size. Our results showed significant
increase in size of NCM with time and reflect aggregation of
micelles in BSA. This phenomenon may be due to protein
adsorption which is undesirable as it can result in fast clear-
ance by the mononuclear phagocyte system.39 It has been
shown that BSA–micelle interaction is typically driven by
hydrophobic aggregation. For instance, micelles with high
density hydrophilic corona experience greater steric stabili-
zation and encounter less BSA interaction.40 Other instances
of polymeric micelle aggregation and interaction with BSA
have been reported in the literature.40,41 In contrast, there
was no appreciable increase in the size of CM following incu-
bation with BSA. One reason may be the less dynamic nature
of CM, which limits the continuous interchange of unimers
thereby reducing the possibility of BSA interacting with the
hydrophobic core. It is also likely that the presence of cova-
lent crosslinks make it difficult for BSA to disrupt micelle
architecture thus preventing BSA–micelle aggregates.
dilution and physiological simulating serum (BSA ꢀ45 mg/
mL). CM size remained unchanged while NCM disintegrated
at a thousand fold dilution. Besides, CM size remained
unchanged in BSA whereas there was a time-dependent
increase in the size of NCM. These results showed CM to be
more stable compared to their non-crosslinked counterparts.
Additionally, bicalutamide-loaded CM were found to be more
potent in inhibiting proliferation of LNCaP prostate cancer
cells compared to NCM regardless of polymer type. In all, we
have demonstrated that these new biodegradable copolymer
systems are potentially useful for cancer therapy. Future
studies on influence of MAC block length, extent of crosslink-
ing efficiency, and ratio of MAC to CB and LA on key micelle
properties are required to generate material design rules
which can be used for customized fabrication of improved
micelle delivery platforms.
ACKNOWLEDGMENT
This work is supported by an Idea Award (W81XWH-10-1-
0969) from the Department of Defense Prostate Cancer
Research Program.
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