BULK AND SOLUTION PROPERTIES OF PEPTIDE-POLYMER CONJUGATES - Biologically-Responsive Hybrid Biomaterials - page 32

to chain composition (as determined by NMR): a strong glutamate presence in
the chain produced cylindrical or spherical micelles, while large hexagonal
platelets resulted from a strong leucine presence. TEM revealed the width of the
platelets to be 200 nm, while data from a combination of CD spectroscopy and x-
ray diffraction suggested the platelet core material was constructed from a three-
dimensional array of leucine zippers.
Deming et al. [119] employed extrusion to produce vesicles from poly( L -
lysine)- b -poly( L -leucine) or PLLys 20-80 -PLLeu 10-30 . The positively charged
poly( L -lysine) portion was included to promote solubility and lend a greater
degree of flexibility to the vesicle membrane. However, the length of this
positively charged portion was shortened (20 to 80 monomers) relative to the
length considered in an earlier study [120] (80 to 380 monomers) so as to
discourage the formation of twisted fibrils due to repulsive interchain reactions.
The copolymer was dissolved in a THF/water solution prior to dialysis against
distilled water. In the considered range of hydrophobic to hydrophilic content,
PLLys 60 - b -PLLeu 20 was selected as the best candidate for further investigation,
due to its formation of giant, unilamellar vesicles (LSCM/TEM). Vesicles
formed from its anionic counterpart - poly( L -glutamic acid)- b -poly( L -leucine) or
PLGA 60 -PLLeu 20 - were also produced for the sake of comparison. The 0.8 Ⱥ m
to 5 Ⱥ m vesicles (size determined by DLS) were extruded through filters with
pore sizes ranging from 0.1 to 1 Ⱥ m, and post-extrusion measurement of the
vesicle size showed good agreement with the pore size. Extrusion was also
found to be an effective way of encapsulating solute (specifically Texas Red-
tagged dextran) within the vesicles. Subsequent osmotic stress tests revealed that
the vesicles were permeable to water, but impermeable to larger molecules such
as sucrose.
The same technique was reported to produce vesicles from poly( L -
arganine) 60 - b -poly( L -leucine) 20 , PLArg 60 - b -PLLys 20 [121]. A substitution of
arganine for lysine was made in order to equip the vesicle membrane with
protein-transduction domains for therapeutic application, specifically
intracellular delivery of vesicle contents (Figure 13). Laser confocal scanning
microscopy (LCSM) revealed rapid cellular uptake for dextran-filled PLArg 60 - b -
PLLys 20 with no apparent disruption to the vesicle or its contents.
The triblock copolymer PLLys- b -PBLG-d7- b -PLLys (where PLLys and
PBLG-d7 are poly( L -lysine hydrochloride) and poly( ȳ -benzyl-d7- L -glutamate)
respectively) was found to form vesicles in water at neutral pH by Hadjichristidis
and collaborators [122]. Vesicle formation occurred within a broad range of
hydrophobic block content - from 19 to 74% of the total molecular weight.
According to the authors, the triblock nature of PBLG-d7- b -PLLys is particularly