pH‐ and temperature‐induced release of doxorubicin from multilayers of poly(2‐isopropyl‐2‐oxazoline) and tannic acid

• Published in: Polymer international Vol. 66; no. 12; pp. 1851 - 1863
• Main Authors: Haktaniyan, Meltem, Atilla, Suleyman, Cagli, Eda, Erel‐Goktepe, Irem
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2017
• Subjects: doxorubicin; hydrogen‐bonded multilayers; layer‐by‐layer; pH‐responsive; poly(2‐isopropyl‐2‐oxazoline); temperature‐responsive
• ISSN: 0959-8103; 1097-0126
• DOI: 10.1002/pi.5458

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 pH 6.5 using the layer‐by‐layer (LbL) technique. We found that multilayers released a minimal amount of DOX at physiological pH due to further ionization of TA with increasing pH and enhanced electrostatic interactions between TA and DOX. In contrast, pH‐induced release of DOX was observed in moderately acidic conditions due to protonation of TA as the acidity increased and electrostatic interactions between TA and DOX decreased. Moreover, we found that raising the temperature from 25 °C to 37.5 °C increased the amount of DOX released from the surface. This can be rationalized with the conformational changes within the multilayers correlated with the lower critical solution temperature behaviour of PIPOX and increased kinetic energy of DOX molecules. Considering the acidic nature of tumour tissues and important biological properties of PIPOX and TA, these multilayers are promising for pH‐ and temperature‐triggered release of DOX from surfaces. © 2017 Society of Chemical Industry Dual responsive layer‐by‐layer films of poly(2‐isopropyl‐2‐oxazoline) and tannic acid releasing doxorubicin at moderately acidic conditions via pH and temperature trigger, while exhibiting minimal release at physiological pH.