Polymeric simvastatin-loaded microsphere delivery system for bone tissue engineering

Mohamed, Nur Aliana Hidayah (2020) Polymeric simvastatin-loaded microsphere delivery system for bone tissue engineering. PhD thesis, University of Nottingham.

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Abstract

Bone graft are useful in the treatment of musculoskeletal injuries/diseases including trauma, bone fractures, painful vertebrae, missing teeth, osteosarcoma, and birth defects. The gold standard for bone graft therapies must be osteoconductive, osteogenic and osteoinductive. Different synthetic and natural biomaterials are being investigated for this purpose. The need to find less sophisticated and more patient-friendly alternatives to the bone graft procedure is a driving force behind recent advances in bone tissue engineering.

In this study, our main aim was to develop a porous, SIM-loaded microsphere delivery system with the capability of sintering in situ. Poly (lactic- co-glycolic acid) (PLGA) was used for this formulation due to its biodegradability, biocompatibility, controllable mechanical properties and good processing capabilities. In order to increase the encapsulation of the drug within the PLGA microparticles, we studied different variables that influenced the stability of the SIM and facilitate controlled and sustained release of it. An optimised procedure for formulating porous and non-porous (SIM-loaded) microspheres was established and the microspheres were extensively characterised.

The relationship between the molecular weight of the PLGA and both SIM release and compressive strength showed significant results for intermediate molecular weight (53 kDa) variety of PLGA thus it was chosen for further work based on balancing the need for retaining sufficient compressive strength and higher release profile. The simvasatain-loaded and porous microspheres were combined as a paste and found to sinter at body temperature (37°C) into scaffolds. Mechanical testing was carried out as to rule the possibility of the scaffold to mimic the bone.

The biocompatibility and osteogenic potential of the scaffolds were investigated using MG-6. Despite SIM gave antiproliferative effect to the cells, MG-63 was chosen as it can give faster results as compared to normal bone cells. Overall studies indicate IMW SIM-NPMP has higher release and increase the MG 63 suppression in the viability studies, whilst the HMW SIM-NPMP showed delay particularly in the viability assay.

The composite PLGA/SIM and porous microspheres combine both porosity and the ability to load and sustain the release of the drug into one system. Moreover, their ability to sinter at body temperature and the possibility to use it as injectable scaffold or applied as a paste demonstrates the dual functionality of the system. This represents a novel approach to delivering SIM for tissue regeneration as presently, there has been no report of the combination of PLGA/SIM microspheres with porous PLGA microspheres as a system that is able to sinter, both post-injection and when packed as a paste, at 37°C. Therefore, the formulation presented in this thesis shows potential for further in vitro and in vivo testing to determine its suitability for bone tissue engineering applications.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Morris, Andrew
Billa, Nashiru
Shakesheff, Kevin
Keywords: simvastatin scaffolds, bone tissue engineering, microparticles, MG 63, musculoskeletal, biocompatibility, osteogenic, PLGA
Subjects: R Medicine > RS Pharmacy and materia medica
Faculties/Schools: UNMC Malaysia Campus > Faculty of Science > School of Pharmacy
Item ID: 60658
Depositing User: MOHAMED, Nur
Date Deposited: 27 Jul 2020 08:51
Last Modified: 27 Jul 2020 08:51
URI: http://eprints.nottingham.ac.uk/id/eprint/60658

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