Glycosaminoglycans (GAGs) are integral part of the closest cellular
environment: they can be found on the cells surface and in the extracellular
matrix, where they interact with different proteins acting as local
regulator of their activity. The use of GAGs in the preparation of protein
delivery nanosystems is, therefore, prominent but so far, underexploited
mainly because of the heterogeneity (composition and molecular
weights) of natural glycans and the multistep procedures needed to
obtain GAGs’ synthetic analogues and diblock copolymers.1 Recently,
we have shown that oxime click reaction can be applied as a straightforward
methodology for the synthesis of poly(ethylene glycol) (PEG)-
hyaluronic acid (HA) diblock copolymers.2 These copolymers formed
nanosized interpolyelectrolyte complexes (45 to 150 nm) by interaction
with poly- L -lysine (PLL).3 Unfortunately, these complexes are not stable
at physiological ionic strength. Herein, we describe a strategy to
overcome this drawback; chondroitin sulphate-b-PEG diblock copolymers
(CS-b-PEG) were obtained using the same oxime click reaction.
The stronger negative charge of sulphate groups (versus the carboxilic
groups present in HA) resulted in the complexes with higher stability:
interpolyelectrolyte complexes between PLL and (CS-b-PEG) are stable
up to 260 mM ionic strenght. Because carbohydrates do not activate Tcells,
we believe that the reported herein complexes have an enormous
potential in both drug delivery and vaccination fields.