Nanoparticle-based formulation for the treatment of osteoarthritis: a tribological study

Simou, Konstantina (2022). Nanoparticle-based formulation for the treatment of osteoarthritis: a tribological study. University of Birmingham. Ph.D.

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Abstract

Osteoarthritis is an incurable disease, which deteriorates the lubrication of the joints, resulting in pain and progressive loss of mobility. A tribological intervention mechanism was established in this thesis to address osteoarthritis development.

The effect of patients’ physical characteristics on the lubrication properties was established from the analysis of osteoarthritic synovial fluid samples. Age above 60 years and Body Mass Index above 30 (obesity) were identified as the dominant risk factors resulting in the degeneration of synovial fluid, and thus, the development of osteoarthritis. Synovial fluid’s viscosity decreased by 58% with age and 38% with BMI, while the shear-thinning index increased by 40% and 7%, respectively. The adhesion energy, which is positively correlated to the coefficient of friction, increased by 172% with age and 234% with Body Mass Index.

Nanoparticle-based formulations were evaluated to remedy the poor lubrication of osteoarthritic joints. The proposed formulations could be delivered to the pathological joints via intra-articular injection, the most effective treatment at the early stages of osteoarthritis. Nevertheless, the current supplements used in intra-articular injection therapy are unable to provide lubrication improvement under low velocities because they are squeezed out of the joints.

Commercially available silica and latex nanoparticles were used to prove the principle that nanoparticles can improve the tribological performance when used on contact surfaces simulating the natural and artificial joint’s contacts. Silica and latex nanoparticles reduced the coefficient of friction by 50.8% and 36.8%, respectively. The maximum reduction in the coefficient of friction is attributed to its surface polishing by
the nanoparticles and was achieved on the rough silicone elastomer. A steel ball-silicone elastomer substrate configuration was used for further testing to replicate the bone-cartilage contact at the beginning of the osteoarthritis when the cartilage is partially removed.

The optimised formulation consisted of 0.5 % w/v biocompatible polymer nanoparticles made of Polymethylmethacrylate, Polycaprolactone, or Polylactic acid dispersed into a 0.1% w/v Hyaluronic acid solution with 0.5% w/v Sodium Dodecyl Sulfate. Nanoparticles reduced the coefficient of friction, owing to the polishing effect. The Hyaluronic acid restored its physiological concentration in the osteoarthritic synovial fluid. Sodium Dodecyl Sulfate enhanced the stability of the formulation by electrostatic interactions. All three biocompatible nanoparticles reduced the coefficient of friction at low velocities. Maximum reduction of the coefficient of friction was achieved at high adsorption of nanoparticles, high Zeta Potential and nanoparticles with low Young’s modulus. As a next step, the biocompatible nanoparticles were loaded with a model drug (Celecoxib). The drug-loaded nanoparticle formulations reduced the coefficient of friction of the human articular cartilage by 32%, prolonged
the release of the drug up to 9 days, and demonstrated excellent biocompatibility, with 82-86% viability to synovial chondrocytes, highlighting their potential use as intra-articular supplements to treat early osteoarthritis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):