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Controlled delivery of antimicrobial and anti-inflammatory agents from un-cemented prosthesis

Al-Otaibi, Hadil Faris 2019. Controlled delivery of antimicrobial and anti-inflammatory agents from un-cemented prosthesis. PhD Thesis, Cardiff University.
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The prevalence of joint replacement procedure increased by more than 119% in the last decade as a result to that the demand for a prosthesis is very likely to increase. Uncemented prosthesis is the first-choice treatment option for patient age less than 68 years, due to its long-term and more stable fixation. The two major limitations that lead to the failure of joint replacement surgery are a prosthetic joint infection and aseptic loosening. To encounter these limitations this study aimed to develop a coating that can control the release of the antimicrobial agent (chlorhexidine) and the anti-inflammatory agent (dexamethasone) to provide prophylaxis from postsurgical inflammation and infection. The antibacterial and anti-inflammatory coating was built initially on titanium nanoparticles followed by the validation on the medical grade Ti alloys surfaces. The multilayer coating was achieved employing a Layer by Layer (LbL) technology incorporating a drug of interest between polyelectrolyte layers of alginate and poly-beta amino esters. Physico-chemical characterisations of the obtained nanoparticles were conducted, and amount of chlorhexidine and dexamethasone released from the multi-layered system was quantified. Cytotoxicity and anti-inflammatory activity were assessed in in-vitro human macrophage cellular model, also cytocompatibility towards human osteoblasts cells were examined. The results showed that chlorhexidine was released in a controlled manner for 60 days from the nanoparticular system providing inhibition of growth for a number of clinically relevant gram- positive and gram-negative bacterial strains. Dexamethasone released for up to 30 days was able to suppress TNF-α and IL-6 production. Study on Ti alloys surfaces confirmed the efficacy of the multi-layered systems. Moreover, no cytotoxic effects were observed towards osteoblasts surrounding prosthetic device confirming not just efficacy but also a safety of the proposed system.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Date of First Compliant Deposit: 17 July 2019
Last Modified: 17 Jul 2019 11:40

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