Abstract

Hyaluronic acid (HA) and chitosan (CH) are biopolymers that are widely used in many biomedical applications and for cosmetic purposes. Their chemical properties are fundamental to them working as drug delivery systems and improving their synergistic effects. In this work, two different protocols were used to obtain zwitterionic liposomes coated with either hyaluronic acid or chitosan. Specifically, the methodologies used to perform vesicle preparation were chosen by taking into account the specific chemical properties of these two polysaccharides. In the case of chitosan, liposomes were first synthesized and then coated, whereas the coating of hyaluronic acid was achieved through lipidic film hydration in an HA aqueous solution. The size and the zeta-potential of the polysaccharide-coated liposomes were determined by dynamic light scattering (DLS). This approach allowed coated liposomes to be obtained with hydrodynamic diameters of 264.4 ± 12.5 and 450.3 ± 16.7 nm for HA- and CH-coated liposomes, respectively. The chemical characterization of the coated liposomal systems was obtained by surface infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopies. In particular, the presence of polysaccharides was confirmed by the bands assigned to amides and saccharides being in the 1500–1700 cm−1 and 800–1100 cm−1 regions, respectively. This approach allowed confirmation of the efficiency of the coating processes, evidencing the presence of HA or CH at the liposomal surface. These data were also supported by time-of-flight secondary ion mass spectrometry (ToF-SIMS), which provided specific assessments of surface (3–5 nm deep) composition and structure of the polysaccharide-coated liposomes. In this work, the synthesis and the physical chemistry characterization of coated liposomes with HA or CH represent an important step in improving the pharmacological properties of drug delivery systems.

Highlights

  • The liposomes were synthesized as reported in the Experimental Section, and the coating methods were performed to obtain liposomes with a modified surface

  • The dynamic light scattering (DLS) experiments were performed after the purification processes

  • Zwitterionic liposomes coated with two polysaccharides: chitosan and hyaluronic acid, which are widely used for biomedical applications, were synthesized and characterized

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Summary

Introduction

Liposomes are self-assembled phospholipid structures showing biocompatibility properties These systems have been applied to improve the bioavailability of hydrophobic bioactive compounds. By modifying the surface of these carriers with polymers, such as polyethylene glycol, they become able to prevent mechanisms of plasma–protein adsorption, interfering with the recognition by the reticuloendothelial system [2,3]. These vesicles are known as stealth liposomes, and their ability to prolong blood circulation, improving the pharmacological effects of drugs, is well documented [4,5,6]. Surface coating with a polymer is able to preserve liposome stability [13], and this behavior depends on the ability of the polymer to adhere to the lipid bilayers [14]

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