C O M M U N I C A T I O N S
applications, in particular, for drug delivery. While polymeric
spherical micelles have already proven to be extremely useful for
therapeutic applications,17 worm micelles are just now emerging
as novel alternatives that provide larger core volume for drug
loading and an ability to flow readily through capillaries and pores
due to their cylindrical shape and flexibility.18 One novel strategy
for drug delivery would be to start with worm micelles and then
progressively degrade into spherical micelles as desired. Further-
n
more, strong effect of temperature, pH, and M on degradation rate
could also be used for controlled drug release.19
In summary, we show that worm micelles self-assemble from
degradable PEO-b-PCL block copolymers and spontaneously
shorten to spherical micelles. Such morphological transition is
triggered by hydrolytic degradation of PCL, governed by an end-
cleavage mechanism that is faster than that in bulk/film. Degradation
Figure 3. Arrhenius plots of OCL worm micelle shortening rate constants,
k, with temperature (4, 25, and 37 °C), R ) 8.314 kJ/mol.
that differ in molecular weight and thus differ in molecular mobility
within worms by far more than 2-fold.12 This suggests that the rate-
limiting process is indeed hydrolysis rather than chain diffusion
and segregation post-hydrolysis.
n
rate can be tuned by temperature, pH, and M , and quantitative
assessment appears to be consistent with the molecular explanation,
whereby the hydroxyl end of the PCL chain localizes to the hydrated
interface of the micelle.
While the end-cleavage of PCL within worm micelles appears
to be consistent with both the chemical and the nanoscale physical
changes, it is also considerably faster than the slow hydrolysis
2
reported for PCL homo/copolymer bulk, particle, or films, that is,
Acknowledgment. We thank F.S. Bates’ group at University
Minnesota for TEM, Chemistry at Penn for NMR and lyophilizing
facilities, and L. Romsted at Rutgers University for discussions.
Support was provided by NSF-MRSEC, Penn-NTI, and NIH.
on the time scale of months-years under the same condition. The
distinction arises with the specific effect of OCL worm micelles
on PCL hydrolysis. As speculated from studies on spherical
micelles,13 the terminal -OH of the hydrophobic PCL block is not
strictly sequestered in the “dry”, hydrophobic core but will tend to
Supporting Information Available: Materials and Methods, OCL
worm micelle contour length distribution and flexibility, GPC, NMR,
transition intermediate, OCL-acetate worm micelles, and data of
shortening rate constants (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
14
be drawn into the hydrated corona. A “micellar catalysis” effect
involving interfacial water plus this likely participation of the
terminal hydroxyl group15 collectively fosters the attack by H
2
O
of the end-ester group nearest the chain terminus. Following this
ester hydrolysis, a new -OH is generated to restart the process of
PCL end-degradation. To provide direct evidence for the crucial
role of the terminal -OH, -OH was modified in OCL1 to an
acetate group by esterification. Worm micelles still formed with
OCL1-acetate, but they showed no significant morphological
change after more than 24 h at 37 °C (Figure S6), by which time
OCL1 worm micelles are completely degraded (Figure 2b).
For both OCL1 and OCL3 worm micelles, shortening rate
constants measured from FM (Table S1) increase exponentially with
temperature, with minimal degradation at 4 °C, but considerable
hydrolysis at the physiological temperature of 37 °C. The temper-
ature dependences fit classic Arrhenius behavior and yield activation
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16
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J. AM. CHEM. SOC.
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