Uğur, Esma
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.


pH- and temperature-induced release of doxorubicin from multilayers of poly(2-isopropyl-2-oxazoline) and tannic acid
Haktanıyan, Meltem; Atilla, Suleyman; Çağlı, Eda; Erel Göktepe, İrem (Wiley, 2017-12-01)
We present a simple strategy to prepare doxorubicin (DOX) containing hydrogen-bonded films of poly(2-isopropyl-2-oxazoline) (PIPOX) and tannic acid (TA) which release DOX in acidic conditions while releasing a minimal amount of DOX at physiological pH. Water soluble complexes of TA and DOX (TA-DOX) were prepared prior to film construction. PIPOX and TA-DOX were deposited at the surface at pH6.5 using the layer-by-layer (LbL) technique. We found that multilayers released a minimal amount of DOX at physiologi...
Bioprocess development for serine alkaline protease production: A review
Çalık, Pınar; Ozdamar, TH (2001-01-01)
This work is the result of the convergence of the research in biochemical reaction engineering and metabolic flux analysis for serine alkaline protease (SAP) production. The genus Bacillus includes a variety of industrially important species that are known to secrete a large number of extracellular proteases and are used among many species as producer of SAP enzyme. Therefore, in the first part of the present article an overview to serine alkaline protease and regulation of its synthesis and secretion in Ba...
Hamamcı, Haluk (1994-02-01)
The production of L(+)-lactic acid using alginate immobilized Rhizopus oryzae in tapered-column fluidized-bed batch reactor was tested and simulated using the kinetic data taken independently in shake-flask cultures. The data show saturation kinetics with substrate and product inhibitions in linear form. Analysis of the kinetic data gave kinetic constants: V-m, 11.04 g lactic acid/(L-bead. h); K-m, 20.9 g glucose/L; and K-i, 365 g glucose/L for lactic acid production. The product inhibition constant, K-p, w...
PH influences intracellular reaction network of beta-lactamase producing Bacillus licheniformis
Çalık, Pınar (Elsevier BV, 2007-09-01)
Effects of pH on metabolic flux distributions in P-lactamase producing Bacillus licheniformis were investigated using metabolic flux analysis, at pH(C) = 6.5, 7.0 and 7.5 controlled-pH conditions. The bioprocess was divided into three periods: Period I (0 < t < 6 h) is the growth phase where beta-lactamase synthesis starts; Period II (6 < t < 8 h) is the transition phase; Period III (8 < t < 12 h) is the stationary phase for the cell-growth where beta-lactamase synthesis increases. The central pathways were...
The Effect Of Multiple Performance Criteria Usage On The Just In Time Production And Total Quality Management Implementation Levels: Findings From Turkey
Aydın, Zehra Berna; Tüzüntürk, Selim; Eryılmaz, Mehmet Eymen (Orta Doğu Teknik Üniversitesi (Ankara, Turkey), 2008-12)
This article examines the effect of the multiple performance criteria usage on Just in Time Production (JIT) and Total Quality Management (TQM) implementation levels. Earlier studies have highlighted that JIT and TQM implementation levels play a major role in the success of organizational performance. Therefore the aim of this study was to determine the significant Balanced Scorecard (BSC) perspectives that may affect JIT and TQM using Logit regression analysis. The analysis process was executed on a sample...
Citation Formats
E. Uğur, “pH and TEMPERATURE RESPONSIVE MULTIPLE DRUG RELEASE from LAYER-by-LAYER MODIFIED MICROPARTICLES,” M.S. - Master of Science, Middle East Technical University, 2022.