Mixtures of hyaluronic acid and liposomes for drug delivery: Phase behavior, microstructure and mobility of liposomes.
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.
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Naila
N
El Kechai
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Sandrine
S
Geiger
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Arianna
A
Fallacara
SPMS, Ecole Centrale Paris, UMR 8580 CNRS, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Ingrid
I
Cañero Infante
UMS IPSIT, Plate-forme d'imagerie cellulaire, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Valérie
V
Nicolas
UMR-S 1159 Inserm/Université Pierre et Marie Curie - Sorbonne Universités "Minimally Invasive Robot-based Hearing Rehabilitation", 16 rue Henri Huchard, 75018 Paris, France.
Evelyne
E
Ferrary
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Nicolas
N
Huang
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Amélie
A
Bochot
Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: florence.agnely@u-psud.fr.
Florence
F
Agnely
D004058:Diffusion; D006820:Hyaluronic Acid / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D012212:Rheology; D013499:Surface Properties
D008081:Liposomes; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-poly-(ethyleneglycol)-2000] (PubChem CID: 406952); Atomic force microscopy; Cholesterol (PubChem CID: 5997); Depletion; Drug delivery; Hydrogel; L-α-phosphatidylglycerol (PubChem CID: 24779550); Phase separation; Phosphatidylcholine (PubChem CID: 52922911); Rhodamine (PubChem CID: 6694); Single particle tracking; Sodium hyaluronate (PubChem CID: 3084049); Stearylamine (PubChem CID: 15793)