Self-assembled thermoresponsive nanostructures of hyaluronic acid conjugates for osteoarthritis therapy

Abstract

Under pathological conditions, joints and skin are often affected by an imbalance in the breakdown and production of hyaluronic acid (HA). The unique biochemical and biomechanical properties provided by HA must be restored for the long-term lubrication and cushioning effects. To overcome the inconvenience of repeated injections and the rapid degradation of exogenous HA treatments, HA is conjugated to a thermosensitive polymer, enabling the spontaneous formation of nanoparticles (HA Nano) at body temperature. Three HA Nano preparations are tested for their injectability, sensitivity to enzymatic degradation and cytocompatibility. One of them is delivered via subcutaneous and intra-articular injections to healthy mice and tested in a murine osteoarthritis (OA) model. It is found to be biocompatible, to offer a prolonged residence time at the injection site, have the ability to protect cartilage, to reduce pro-inflammatory cytokines and to preserve epiphysis thickness. In this study, HA Nano spontaneously forms nanoparticles at body temperature in vivo and is a promising candidate for the next generation of the sustainable/long-lasting treatment of OA and potentially also dermatological conditions.

Hyaluronic Acid in the Third Millennium

“…Another promising type of drug delivery system, which can be formulated with HA and its derivatives of synthesis, is represented by nanoparticles. Hyaluronan can be a constituent element of nanoparticles [192,193], but can also be used to cover nanoparticles, in order to improve the targeting efficiency and the therapeutic action of the encapsulated drugs [194]. HA-nanoparticles are being investigated for a number of administration routes and customized applications: for example, HA-Flt1 peptide conjugate nanoparticles might represent a next-generation pulmonary delivery carrier for dexamethasone in the management of asthma [193], while chitosan nanoparticles coated with HA and containing betamethasone valerate have displayed a great potential for the topical treatment of atopic dermatitis [194].…”

Therapeutic effect and mechanisms of intra-articular injections of microRNA-140-5p on early-stage osteoarthritis in rats

“…In order to enhance the cartilage-targeting delivery efficiency and minimize dosage requirements, construction of carriers with good safety, precise cartilage-targeting and high delivery efficiency is essential. A number of delivery vectors for miRs have been reported, such as adenoviruses, collagen scaffolds and hydrogels [30,31], and biochemical modifications that can selectively bind to cartilage or play specific biological functions may further improve the vectors. For example, Li et al reported that N-Cadherin peptidomimetic modified self-assembling polypeptide nanomaterials enhances the chondrogenic differentiation of mesenchymal stem cells (MSCs) [32].…”

Nanoparticles Containing Hyaluronan Acid and Astragalus Polysaccharides for Treating Osteoarthritis

“…The preparation of nanoparticles was performed as described previously [11]. We followed and modified the methods of Maudens et al [12]. 1,2-Dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) and 1,2-dilauroyl-sn-glycero-3glycerol (DLPG) were from Avanti Polar Lipids Inc. (Alabaster, AL, USA).…”