Osteoarthritis is one of the most widespread diseases worldwide, with a progressive damage to cartilage and bone. In this context, the choice of biocompatible materials mimicking the cellular microenvironment is of the utmost importance to develop new drug carriers. Cyclodextrins (CDs) and hyaluronic acid (HA) are promising candidates for intra-articular injection in the joint synovial fluid because of the high biocompatibility and effectiveness of HA, empowered by the presence of the CD units able to entrap therapeutic agents for the regenerative process. Nano and micro scale polymeric assemblies based on cationic ?-CD polymers (PolyCDNH3+ or PolyCDNR3+) and HA have been developed by using both supramolecular and/or covalent approaches. Supramolecular nanoassemblies made from PolyCDNH3+ were obtained by using a crosslinker bearing two terminal adamantane moieties. Spongy hydrogels based on PolyCDNR3+/HA were prepared through amide formation. The nanoassemblies were loaded with fluorescent probe, with diclofenac and were characterized by complementary spectroscopic techniques including 1H-NMR, UV-Vis, steady-state and time-resolved fluorescence, DLS and ?-potential measurement. Release profiles were investigated in vitro in media mimicking the physiological conditions to ensure control over time and efficacy. Biocompatibility studies were performed by placing primary human bone marrow-derived mesenchymal stromal cells in contact with the nanosystems and testing cell viability by WST-1 assay. With these premises, this study might open novel routes to exploit original CD-based nanobiomaterials for OA treatment.
Novel cyclodextrin based nanoplatforms for the treatment of osteoarthritis
Annalaura Cordaro;Roberto Zagami;
2019
Abstract
Osteoarthritis is one of the most widespread diseases worldwide, with a progressive damage to cartilage and bone. In this context, the choice of biocompatible materials mimicking the cellular microenvironment is of the utmost importance to develop new drug carriers. Cyclodextrins (CDs) and hyaluronic acid (HA) are promising candidates for intra-articular injection in the joint synovial fluid because of the high biocompatibility and effectiveness of HA, empowered by the presence of the CD units able to entrap therapeutic agents for the regenerative process. Nano and micro scale polymeric assemblies based on cationic ?-CD polymers (PolyCDNH3+ or PolyCDNR3+) and HA have been developed by using both supramolecular and/or covalent approaches. Supramolecular nanoassemblies made from PolyCDNH3+ were obtained by using a crosslinker bearing two terminal adamantane moieties. Spongy hydrogels based on PolyCDNR3+/HA were prepared through amide formation. The nanoassemblies were loaded with fluorescent probe, with diclofenac and were characterized by complementary spectroscopic techniques including 1H-NMR, UV-Vis, steady-state and time-resolved fluorescence, DLS and ?-potential measurement. Release profiles were investigated in vitro in media mimicking the physiological conditions to ensure control over time and efficacy. Biocompatibility studies were performed by placing primary human bone marrow-derived mesenchymal stromal cells in contact with the nanosystems and testing cell viability by WST-1 assay. With these premises, this study might open novel routes to exploit original CD-based nanobiomaterials for OA treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
