Gentamicin-Loaded Poly (Lactic Acid) Microsphere Corporated Chitosan-Coated Carbonate Apatite Scaffold
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Date
2019-05-01
Authors
Mamat @ Mohamad Nor, Normahira
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
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.