Date

2022-8-10

Author

Uğur, Esma

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This thesis study reports on preparation of layer-by-layer (LbL)-modified microparticles based on temperature responsive poly(2-isopropyl-2-oxazoline) (PIPOX) and pH-responsive Tannic Acid (TA), displaying dual responsive multiple drug release. PIPOX, exhibiting lower critical solution temperature (LCST)-type phase behavior, was synthesized through cationic ring opening polymerization (CROP). PIPOX was then partially hydrolyzed in concentrated acid medium, resulting in poly(2-isopropyl-2-oxazoline-r-polyethylene imine) (PIPOX-PEI). Multilayer films of PIPOX-PEI and TA were produced using LbL self-assembly method through hydrogen bonding interactions between carbonyl groups of PIPOX and phenolic hydroxyl groups of TA together with electrostatic interactions between secondary amine groups of PEI and phenolate groups of TA. Covalent crosslinks were introduced between the layers upon treatment with NaIO4 solution. Stability of noncross-linked and cross-linked multilayers were contrasted with respect to stability at physiologically related pH and temperature conditions. Stability and water uptake of non-crosslinked PIPOX-PEI and TA multilayers were found to depend on pH and temperature. The highest water uptake was recorded at pH 7.4 and 37℃ when hydrogen bonding interactions between PIPOX-PEI and TA was partially disrupted due to ionization of TA and conformational transition of PIPOX occured above its critical temperature. On the contrary, crosslinked PIPOX-PEI and TA multilayers did not show water uptake under similar conditions. On the other hand, stability of cross-linked multilayers was remarkably higher at basic conditions compared to noncross-linked films. The fundamental information generated on LbL films constructed on 2D substrates has formed a basis to construct multilayers on 3D colloidal microparticles. Two different CaCO3 microparticles were used, i.e. bare and Curcumin (CUR) loaded. Bare CaCO3 microparticles were LbL-modified using TA and PIPOX-PEI, cross-linked using NaIO4 and made hollow by dissolving the CaCO3 core using EDTA solution. The hollow interior and the capsule wall were used for CUR and Doxorubicin (DOX) loading. CUR-loaded microparticles were LbL-modified using TA and PIPOX-PEI and post-loaded with DOX. Two different microparticles were contrasted with respect to drug loading and release properties. In addition, the effects of pH and temperature on release of CUR and DOX from both types of microparticles were examined. Finally, preliminary results on synergistic effect of CUR and DOX and potential of these LbL particles for anticancer applications were demonstrated.

Subject Keywords

Poly(2-isopropyl-2-oxazoline), Tannic Acid, Temperature Responsive, pH Responsive, Multiple Drug Release

URI

https://hdl.handle.net/11511/99738

Collections

Graduate School of Natural and Applied Sciences, Thesis