Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes

Abstract

Although osteoarthritis (OA) is a chronic inflammatory degenerative disease affecting millions of people worldwide, the current therapies are limited to palliative care and do not eliminate the necessity of surgical intervention in the most severe cases. Several dietary and nutraceutical factors, such as hydroxytyrosol (Hyt), have demonstrated beneficial effects in the prevention or treatment of OA both in vitro and in animal models. However, the therapeutic application of Hyt is limited due to its poor bioavailability following oral administration. In the present study, a localized drug delivery platform containing a combination of Hyt-loading chitosan nanoparticles (Hyt-NPs) and in situ forming hydrogel have been developed to obtain the benefits of both hydrogels and nanoparticles. This thermosensitive formulation, based on Pluronic F-127 (F-127), hyaluronic acid (HA) and Hyt-NPs (called Hyt@tgel) presents the unique ability to be injected in a minimally invasive way into a target region as a freely flowing solution at room temperature forming a gel at body temperature. The Hyt@tgel system showed reduced oxidative and inflammatory effects in the chondrocyte cellular model as well as a reduction in senescent cells after induction with H2O2. In addition, Hyt@tgel influenced chondrocytes gene expression under pathological state maintaining their metabolic activity and limiting the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features. Hence, it can be concluded that the formulated hydrogel injection could be proposed for the efficient and sustained Hyt delivery for OA treatment. The next step would be the extraction of “added-value” bioactive polyphenols from by-products of the olive industry, in order to develop a green delivery system able not only to enhance the human wellbeing but also to promote a sustainable environment.

In Vitro and Ex Vivo Evaluation of Mangifera indica L. Extract-Loaded Green Nanoparticles in Topical Emulsion against Oxidative Stress and Aging

“…The DPPH assay results indirectly prove the efficiency of the M-Ext against aging and oxidative stresses due to the presence of TPC and TFC. Outcomes based on DPPH activity of M-Ext, M-Ext is suitable as an antiaging or antioxidative stress agent in pharmaceutical or pharmaceutical formulations [ 14 , 53 ]. Therefore, it could be a new approach to formulate green formulation to cope with early aging and oxidative stresses that results in thwarted life.…”

“…These compounds have good potency to control the overproduction of FRs [ 10 ]. M. indica crude extract (peels and kernel) showed tyrosinase inhibition [ 11 , 12 ] and reversible inhibition of elastase and collagenase enzymes [ 13 ], which makes it appropriate for use in pharmaceutical and cosmetic products to treat dermatitis, psoriasis, acne, and premature skin aging [ 14 ]. The topical application of M. indica kernel extract is limited due to its low shelf life, poor solubility, and low skin permeation [ 15 ].…”

“…Topical nanolipid carriers (NLCs) have the potency to address the limitations related with conventional topical formulations loaded with natural extracts via such physicochemical properties as their controllable and ultrasmall size, more surface area, functionalizable structure, and increased stability [ 14 ]. Such delivery systems amend the bioactive compound to perform longer and more effectively within the body [ 16 ].…”

Thermosensitive In Situ Gels for Joint Disorders: Pharmaceutical Considerations in Intra-Articular Delivery

“…Hydrogels and nanoparticles were combined to develop a drug delivery platform of hydroxytyrosol, composed of hyaluronic acid and Pluronic F127. On injection, the thermosensitive formulation underwent a sol–gel transition at body temperature with resultant sustained action [ 92 ].…”

Characterization and Encapsulation of Natural Antioxidants: Interaction, Protection, and Delivery

“…The smart hydrogel was further used to encapsulate hydroxytyrosol-loaded chitosan nanoparticles for the treatment of osteoarthritis. The in vitro study demonstrated that the combination of hydrogels and antioxidant-loaded nanoparticles showed potential use in the treatment of the chronic inflammatory degenerative disease [ 18 ].…”