The
amphiphilic heterograft copolymers bearing biocompatible/biodegradable
grafts [poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline)-g-poly(d-l-lactic acid)/poly(2-ethyl-2-oxazoline)]
were synthesized successfully by the combination of cationic ring-opening
polymerization and click chemistry via the ⟨“grafting
to”⟩ approach. The challenge of this synthesis was to
graft together hydrophobic and hydrophilic chains on a hydrophilic
platform based on PMeOx. The efficiency of grafting
depends on the chemical nature of the grafts and of the length of
the macromolecular chains. The self-assembly of these polymers in
aqueous media was investigated by DLS, cryo-TEM, and SANS. The results
demonstrated that different morphologies were obtained from nanospheres
and vesicles to filaments depending on the hydrophilic weight ratio
in the heterograft copolymer varying from 0.38 until 0.84. As poly(2-ethyl-2-oxazoline)
is known to be thermoresponsive, the influence of temperature rise
on the nanoassembly stability was studied in water and in a physiological
medium. SANS and DLS measurements during a temperature ramp allowed
to show that nanoassemblies start to self-assemble in “raspberry
like” primary structures at 50 °C, and these structures
grow and get denser as the temperature is increased further. These
amphiphilic heterograft copolymers may include hydrophobic drugs and
should find important applications for biomedical applications which
require stealth properties.