BULK AND SOLUTION PROPERTIES OF PEPTIDE-POLYMER CONJUGATES - Biologically-Responsive Hybrid Biomaterials - page 25

the polypeptide portion of the material forms a corona or shell around a core of
polymer.
Three decades ago, Nakajima et al. [85] first reported the formation of
micelles in organic solvents from a polypeptide copolymer material consisting of
a coiled poly( trans -1,4-butadiene) block flanked by two rod-like blocks of
poly( ȳ -benzyl L -glutamate) to form PBLG 53-188 - block -PB 64 - block -PBLG 53-188
(subscripts indicate average number of repeat units). Contact-angle-based
estimation of the surface tension of the component copolymer blocks, in addition
to consideration of their interfacial free energy, enabled thermodynamic
calculation of micellar structures likely to result from various copolymer
compositions. The presence of these predicted morphologies - spherical,
cylindrical, and lamellar structures with calculated micelle dimensions of 25 to
45 nm - was confirmed by transmission electron microscope (TEM). A later
study [86] revealed similar behavior for a different rod-coil block copolymer
with rod-like poly(γ-methyl L -glutamate) (PMLG) dissolved in the continuous
phase, suggesting that the aggregation of such samples may be handled similarly
to those of conformationally isotropic samples [87].
The past decade has seen micellar structures obtained in water using
hydrophilic poly(amino-acids) that exhibit secondary structure transitions similar
to those of proteins. For example, the hydrodynamic radius of polyisoprene- b -
poly( L -lysine) (PI 49 - b -PLLys 123 ) micelles nearly doubled following a decrease of
pH from 11 to 6 in saline solution [88]. At pH 11, the poly( L -lysine) presented
α-helical structure corresponding to a hydrodynamic radius of 23 nm
(determined by dynamic light scattering or DLS). At pH 6, micelle radius
swelled to 44 nm due to a shift from helical to coil PLLys structure. For
polybutadiene- b -poly( L -glutamate) (PB- b -PLGA) with similarly sized segments
(PB 48 - b -PLGA 114 compared to PI 49 - b -PLLys 123 ) the effect was significantly
smaller at about 8% [89]. The minimal pH-induced size response in the PB- b -
PLGA system may be a consequence of folding or disruption [90] of the PLGA
helices, whereas the PLLys helices may be in a more extended state. Moreover,
addition of 2,2'-(ethylenedioxy)bisethylamine to PB 48 - b -PLGA 114 and of glutaric
dialdehyde to PI 49 - b -PLLys 178 promoted crosslinking in either system [91],
without affecting aggregate size or morphology.
Micelle formation was observed from the material poly( L -cysteine)- b -poly( L -
lactide) or PLCys- b -PLLac [92]. In this case, addition of dithiothreitol (DTT)
reversibly removed cross-linking of the hydrophilic poly( L -cysteine) corona or
shell through the cleaving of disulfide bonds into two separate thiol groups.
Extension of the polycysteine segments resulted in a slight, but measurable,