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

Haktanıyan M., Atilla S., Çağlı E., Erel Göktepe İ.

POLYMER INTERNATIONAL, vol.66, pp.1851-1863, 2017 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 66
  • Publication Date: 2017
  • Doi Number: 10.1002/pi.5458
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.1851-1863
  • Keywords: layer-by-layer, pH-responsive, temperature-responsive, poly(2-isopropyl-2-oxazoline), doxorubicin, hydrogen-bonded multilayers, HYDROGEN-BONDED MULTILAYERS, DRUG-DELIVERY, POLYMER CAPSULES, PHASE-TRANSITION, AQUEOUS-SOLUTION, BLOCK-COPOLYMER, FILMS, POLYPHENOLS, DOXORUBICIN, POLY(2-OXAZOLINE)S


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 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 degrees C to 37.5 degrees 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. (c) 2017 Society of Chemical Industry