Emulsion assisted nonsteroidal anti-inflammatory drug delivery system for the osteoarthritis treatment

Saeedi, Tahani 2023. Emulsion assisted nonsteroidal anti-inflammatory drug delivery system for the osteoarthritis treatment. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Osteoarthritis (OA) is one of the considerable chronic health conditions worldwide. In the UK, 8.75 million people were receiving OA treatment. Currently, there are no disease-modifying drugs, and treatment relies on the management of pain associated with OA. The delivery of OA drugs is challenging because the cartilage is dense, avascular (i.e., has no blood vessels), and relies on diffusion to transport nutrients and drugs to the cells. Moreover, cartilage matrix is composed of anionic proteoglycans that can repel negatively charged drugs, making it difficult for OA drugs to penetrate through the matrix and reach the target cells. Additionally, most OA drugs are hydrophobic, so an appropriate technique is required to deliver them inside cartilage. A novel and efficient emulsion-based local delivery of OA drugs coated with poly beta-amino ester polymers (POLY-X) into cartilage was proposed. In this project, nonsteroidal anti-inflammatory drugs as a model drug for OA treatment were examined. The characterization of the developed delivery system and its efficacy in native (nontreated) and glycosaminoglycan (GAG) depleted cartilage was assessed by measuring the zeta potential and size, amount of drug uptake and retention in the cartilage. In addition, the ability of the developed drug delivery system to inhibit cytokine (IL-1α) induced glycosaminoglycan and collagen degradation, as well as the loss of cell viability in cartilage explants were tested. The data showed that the developed emulsion delivery system exhibited enhanced and prolonged drug localisation not only on non-treated cartilage tissues but also on GAG depleted sample resulting in a higher amount of drug uptake and retention in cartilage compared to the control, and the difference was statistically significant (p < 0.05). Furthermore, the developed emulsion delivery system protects the viability of the chondrocyte cell and provides a significant increased (p <0.01) in glycosaminoglycan and collagen content compared to IL-1α treated cartilage and similar to untreated control. The percentage of sGAG and collagen loss was 3 to 5 times higher in IL-1α treated cartilage compared to the untreated and developed drug delivery system treated groups. This study proved that modified emulsion-based therapy could provide a substantial improvement in the treatment of OA to maintain cartilage properties and improve OA outcomes.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	16 August 2023
Last Modified:	16 Aug 2023 09:50
URI:	https://orca.cardiff.ac.uk/id/eprint/161828

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