Mamat @ Mohamad Nor, Normahira (2019) Gentamicin-Loaded Poly (Lactic Acid) Microsphere Corporated Chitosan-Coated Carbonate Apatite Scaffold. PhD thesis, Universiti Sains Malaysia.
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Abstract
The development of multifunctional bone scaffold with the controlled drug delivery functions accelerates bone regeneration. However, sustaining drug release rate with desired initial burst release are main factors that influence a targeted antibiotic release to prevent infection at defect site. The overall aim of this study is to develop carbonate apatite (CO3Ap) scaffold and incorporated with drug-loaded poly (lactic acid) (PLA) microsphere. Firstly, CO3Ap was fabricated by transforming β TCP scaffold via hydrothermal treatment. The transformation was evaluated based on 3 and 5 molar concentrations of Na2CO3 solution and treatment time for 3, 5 and 7 days. CO3Ap scaffold was then coated by various chitosan concentrations (0.5%, 1% and 2%) to improve compressive strength. Silane coupling agent was utilized to enhance the interfacial adhesion between scaffold and coating layer via its chemical link. Secondly, gentamicin-loaded PLA microspheres was fabricated by double emulsion and solvent evaporation method. Due to hydrophobicity of PLA microspheres, hydrolysis by using alkaline treatment which assisted by ethanol was studied to improve PLA surface functionality. Finally, in order to incorporate the drug into fabricated scaffold, gentamicin as antibiotic of broad-spectrum bacteria activity was used. Three methods of loading gentamicin into scaffolds were investigated; direct loading, coated with chitosan and coated with gentamicin-loaded PLA microsphere in chitosan. Results on the CO3Ap scaffold showed that carbonate content with 11 wt.% was obtained for 5 days treatment using 5 molar Na2CO3. Coating scaffold with aided silane treatment improved compressive strength 2 times higher than without treatment. The presence of Si-OH group also enhanced apatite growth on the coated scaffold for 28 days bioactivity test. Use of ethanol in alkaline treatment improved hydrophilicity of PLA microsphere and reduced protein adsorption while maintained higher drug encapsulation efficiency. A controlled drug delivery by incorporation of gentamicin-loaded PLA microsphere into CO3Ap scaffold increased drug release rate. This shows gentamicin-loaded PLA microsphere in coated scaffold played beneficial role in combating infection for prolonging time. It is found that adherence of gentamicin-loaded PLA microsphere on scaffold not hindered the apatite growth for 28 days investigation. In fact, more roughness on CO3Ap scaffold contributed by attachment of PLA microspheres enhanced more anchorage to the cells. Cell viability was improved for 7 days cell culture on that scaffold. In the present study, results showed that, gentamicin-loaded PLA microspheres incorporated in coated CO3Ap scaffold represents the best scaffold system which improved antibiotic release in a localised drug delivery. The system holds great potential in provide mechanical support for tissue regeneration with similar bone mineral composition.
| Item Type: | Thesis (PhD) |
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| Subjects: | T Technology T Technology > TN Mining Engineering. Metallurgy |
| Divisions: | Kampus Kejuruteraan (Engineering Campus) > Pusat Pengajian Kejuruteraan Bahan & Sumber Mineral (School of Material & Mineral Resource Engineering) > Thesis |
| Depositing User: | Mr Engku Shahidil Engku Ab Rahman |
| Date Deposited: | 30 Dec 2022 04:36 |
| Last Modified: | 30 Dec 2022 04:36 |
| URI: | http://eprints.usm.my/id/eprint/56166 |
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