4.7 Article

Hybrid systems combining liposomes and entangled hyaluronic acid chains: Influence of liposome surface and drug encapsulation on the microstructure

Journal

JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 628, Issue -, Pages 995-1007

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2022.07.146

Keywords

Cryo-electron microscopy; Depletion; Drug encapsulation; Hyaluronic acid; Hybrid systems; Liposomes; Microstructure; Semi-dilute entangled regime; Small angle neutron scattering; Surface

Funding

  1. Ministere de l'Enseignement Superieur, de la Recherche et de l'Innovation [2017-110]
  2. ANR (The French National Research Agency) [ANR-15-CE19-0014-02]
  3. French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-05]
  4. Agence Nationale de la Recherche (ANR) [ANR-15-CE19-0014] Funding Source: Agence Nationale de la Recherche (ANR)

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The microstructure and interactions of hybrid systems formed by mixtures of hyaluronic acid and liposomes were investigated, and it was found that the surface properties of liposomes play a crucial role in determining their structure.
Mixtures of hyaluronic acid (HA) with liposomes lead to hybrid colloid-polymer systems with a great interest in drug delivery. However, little is known about their microstructure. Small angle neutron scattering (SANS) is a valuable tool to characterize these systems in the semi-dilute entangled regime (1.5% HA) at high liposome concentration (80 mM lipids). The objective was to elucidate the influence of liposome surface (neutral, cationic, anionic or anionic PEGylated), drug encapsulation and HA concentration in a buffer mimicking biological fluids (37 degrees C). First, liposomes were characterized by SANS, cryo-electron microscopy, and dynamic light scattering and HA by SANS, size exclusion chromatography, and rheology. Secondly, HA-liposome mixtures were studied by SANS. In HA, liposomes kept their integrity. Anionic and PEGylated liposomes were in close contact within dense clusters with an amorphous organization. The center-to-center distance between liposomes corresponded to twice their diameter. A depletion mechanism could explain these findings. Encapsulation of a corticoid did not modify this organization. Cationic liposomes formed less dense aggregates and were better dispersed due to their complexation with HA. Liposome surface governed the interactions and microstructure of these hybrid systems. (C) 2022 Elsevier Inc. All rights reserved.

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