In this work, a new amphiphilic derivative made of 10-undecylenic acid grafted to hyaluronan was prepared by mixed anhydrides. The reaction conditions were optimized, and the effect of the molecular weight (Mw), reaction time, and the molar ratio of reagents was explored. Using this methodology, a degree of substitution up to 50% can be obtained. The viscosity of the conjugate can be controlled by varying the substitution degree. The physicochemical characterization of the modified hyaluronan was performed by infrared spectroscopy, Nuclear Magnetic Resonance, Size-Exclusion Chromatography combined with Multiangle Laser Light Scattering (SEC-MALLS), and rheology. The low proton motility and self-aggregation of the amphiphilic conjugate produced overestimation of the degree of substitution. Thus, a novel method using proton NMR was developed. Encapsulation of model hydrophobic guest molecules, coenzyme Q10, curcumin, and α-tocopherol into the micellar core was also investigated by solvent evaporation. HA-UDA amphiphiles were also shown to self-assemble into spherical nanostructures (about 300 nm) in water as established by dynamic light scattering. Furthermore, HA-UDA was crosslinked via radical polymerization mediated by ammonium persulphate (APS/TEMED). The cross-linking was also tested by photo-polymerization catalyzed by Irgacure 2959. The presence of the hydrophobic moiety decreases the swelling degree of the prepared hydrogels compared to methacrylated-HA. Here, we report a novel hybrid hyaluronan (HA) hydrogel system of physically encapsulated active compounds and chemical crosslinking for potential applications in drug delivery.

• Keywords
• amphiphiles, crosslinking, esterification, hyaluronan, hydrogels,
• Publication type
• Journal Article MeSH

This review shows the steps toward material selection focalized on the design and development of medical devices based on hyaluronan (HA). The selection is based on chemical and mechanical properties, biocompatibility, sterilization, safety, and scale-up costs. These facts play a vital role in the industrialization process. Approved medical devices containing-HA are illustrated to identify key parameters. The first part of this work involves the steps toward a complete characterization of chemical and mechanical aspects, reproducibility of the processes and scale up. In a second stage, we aimed to describe the preclinical in vitro and in vivo assays and selected examples of clinical trials. Furthermore, it is important to keep in mind the regulatory affairs during the research and development (R&D) using standardization (ISO standards) to achieve the main goal, which is the functionality and safety of the final device. To keep reproducible experimental data to prepare an efficient master file for the device, based on quality and recorded manufacturing data, and a rigorous R&D process may help toward clinical translation. A strong debate is still going on because the denominated basic research in HA field does not pay attention to the purity and quality of the raw materials used during the development. So that, to achieve the next generation of devices is needed to overcome the limitations of state of art in terms of efficacy, biodegradability, and non-toxicity.

• Keywords
• FDA, chemical modification, clinical data, cross-linked, hyaluronan, hydrogel, preclinical data, risk management,
• Publication type
• Journal Article MeSH
• Review MeSH