Development of novel intra-articular injection formulations based on porous artificial cartilage

Han, Xiaoyu (2023). Development of novel intra-articular injection formulations based on porous artificial cartilage. University of Birmingham. Ph.D.

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Abstract

Osteoarthritis (OA) patients suffer from joint pain during daily activities, which affects more than 40% of people older than 70 years old. The intra-articular injection (IAI) with drug delivery systems (DDSs) has been developed for OA treatment, which relieves pain feeling for patients but is difficult to stay in the articular space sustainedly. As different materials has been used as the drug carriers in the DDSs, considered to the nanometre-sized cartilage pores on the surface, the present thesis aims to focus on the nanoparticles and improve the nanoparticle-based solution lubrication via in vitro tribological measurement on an artificial cartilage system.
In this thesis, an artificial cartilage model was fabricated by porous polydimethylsiloxane (PDMS) coated with polyvinyl alcohol (PVA), which was applied as the substrate of the lubrication system in this thesis. The porosity of artificial cartilage varies from 54.6 ± 1.1% to 81.7 ± 0.7%, which is controlled by the sodium chloride fraction used in porous PDMS preparation. In combination with sodium chloride fraction and curing agent ratio, it is possible to control Young’s modulus and coefficient of friction (CoF). By increasing the sodium chloride fraction or curing agent ratio of porous PDMS, it was found that the Young’s modulus of porous PDMS decreases and the CoF of porous PDMS surface increases. With the coating of PVA, the porous PDMS surface was modified to hydrophilic as fresh cartilage, which increases the Young’s modulus and decreases the CoF of the models. The structural, elastic, and tribological characteristics of the set of artificial scaffolds are aligned with values for the different OA stages (stages 0 - 3) of degeneration of the cartilage tissues, as defined by the International Cartilage Repair Society (ICRS).
Using the artificial cartilage models developed by PDMS coated with PVA, the nanopar- ticle solution parameters were found to impact the lubrication behaviour. The CoF of the nanoparticle solution was found to increase while the normal load increased, and the increase of nanoparticle size increases the CoF on the PDMS coated with PVA, which was increased from 0.042 ± 0.005 to 0.060 ± 0.025 when the size increased from 152.40 nm to 256.00 nm. A critical concentration of nanoparticles was found with the lowest CoF. While the nanoparticle concentration increases, the CoF of the nanoparticle solution decreases when the concentration is lower than the critical concentration and increases when higher.
Synthesised nanogels provided more different choices of nanoparticles to be compared in the present study. Compared to different types of nanogels, the nanogel prepared under the condition of the microfluidic chip with 2 bars pressure showed the lowest CoF. Moreover, the nanogel showed much higher efficiency than silica nanoparticles in reducing CoF of poroelastic surface, including artificial models and human osteoarthritis cartilage. At the concentration of 0.1 mg ml−1, the CoF of nanogels (AEL 04) on human cartilage varies from 0.005 to 0.008, and the CoF of silica nanoparticles (Aerosil 150) is from 0.007 to 0.013. In addition, osteoarthritis articular cartilage mechanical properties were measured in this thesis with a wide range of Young’s modulus and CoF; and the porous structure of cartilage were exhibited in AFM and SEM images.
Overall, this thesis replicated the articular cartilage with porous polymer materials, which fabricated a consistent artificial cartilage model with controllable mechanical proper- ties. Moreover, the thesis studied the lubrication system of nanosized particles. The findings advance the understanding of nanofluid tribological behaviour on the artificial cartilage and confirm the better lubrication efficiency of nanogels and the best type of nanogel, which provides guidance for the IAI formulation improvement and the drug carrier choice in future work.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):