Abstract
Osteoarthritis is the most widespread joint-affecting disease. The management of persistent pain remains inadequate and demands new therapeutic strategies. In this study, we explored the pain relieving and protective properties of a single intra-articular (i.a.) injection of khellin loaded in nanovesicles (K-Ves) based on ascorbyl decanoate plus phosphatidylcholine in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) treatment. The developed nanovesicles (approximately 136 nm) had a narrow size distribution (PdI 0.26), a good recovery (about 80%) and a worthy encapsulation efficiency (about 70%) with a ζ-potential of about −40 mV. The stability of K-Ves was assessed in simulated synovial fluid. Seven days after the articular damage with MIA, both K-Ves and a suspension of khellin (K, 50 μL) were i.a. injected. K-Ves significantly counteracted MIA-induced hypersensitivity to mechanical noxious (paw pressure test) and non-noxious stimuli (von Frey test) and significantly reduced the postural unbalance related to spontaneous pain (incapacitance test) and the motor alterations (beam balance test) 7 and 14 days after the i.a. injection. K was partially active only on day 7 after the treatment. The histology emphasized the improvement of several morphological factors in MIA plus K-Ves-treated animals. In conclusion, K-Ves could be successfully used for the local treatment of osteoarthritis.
Highlights
Osteoarthritis (OA) refers to a clinical syndrome of joint pain accompanied by varying degrees of functional limitation and a reduced quality of life
The formulation containing 13.2 mg/mL ascorbyl decanoate was selected for further investigations because of the small size, optimal for enhanced permeation and distribution, together with a little PDI in order to achieve constant in vivo performances and obtain a successful therapy
The main limitations to the successful clinical use of natural products are represented by their low water solubility and stability and poor biopharmaceutical characteristics, which can be overcome by different technological approaches, especially the development of nanocarriers [34]
Summary
Osteoarthritis (OA) refers to a clinical syndrome of joint pain accompanied by varying degrees of functional limitation and a reduced quality of life. It is the most common form of arthritis and one of the leading causes of pain and disability worldwide, characterized by the gradual development of mutable joint pain, swelling and difficulty and loss of motion [1,2]. Early-stage drug intervention can reduce the development of osteoarthritis and structurally and functionally repair the joints but the clinical efficacy of conventional therapeutic approaches is very poor, principally due to the formulations, which are not able to efficiently penetrate the cartilage tissues and deliver proper drug doses over time, determining minimal off target effects.
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