Mixtures of hyaluronic acid and liposomes for drug delivery: Phase behavior, microstructure and mobility of liposomes
Résumé
Hyaluronic acid liposomal gels have previously demonstrated in vivo their great potential for drug
delivery. Elucidating their phase behavior and structure would provide a better understanding of their
use properties. This work evaluates the microstructure and the phase behavior of mixtures of hyaluronic
acid (HA) and liposomes and their impact on the vesicle mobility. HA concentration and surface
properties of liposomes (positively or negatively charged, neutral, with a polyethylene glycol corona) are
varied while the liposome concentration remains constant. Below the entanglement concentration of HA
(0.4%), the mixtures exhibit a depletion phase separation except for positively charged liposomes that
interact with anionic HA through attractive electrostatic interactions. At high HA concentration, no
macroscopic phase separation is observed, except a slight syneresis with cationic liposomes. The
microstructure shows aggregates of liposomes homogeneously distributed into a HA network except for
PEGylated liposomes, which seem to form bicontinuous interpenetrating networks. The diffusion of
liposomes is controlled by HA concentration and their surface properties. Finally, PEGylated liposomes
display the highest mobility at high HA concentration (2.28%) both macro- and microscopically. The
microstructure of HA-liposomes mixtures and the diffusion of liposomes are key parameters that must be
taken into account for drug delivery.