Self-assembling PVA-F127 thermosensitive nanocarriers with highly sensitive magnetically-triggered drug release for epilepsy therapy in vivo

Hsin Yang Huang, Shang Hsiu Hu, Chih Shang Chian, San-Yuan Chen*, Hsin Yi Lai, You Yin Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Self-assembling, crosslinker-free, highly thermosensitive nanocarriers (TSNCs) were synthesized by the incorporation of iron oxide nanoparticles and hydrophobic drug molecules into a thermosensitive matrix composed of PEO-PPO-PEO (F127) triblock-copolymer and polyvinyl alcohol (PVA) using a mini-emulsion process. The addition of PVA significantly contributes to the stability of the thermosensitive PVA-F127 nanocarriers and reduces drug leakage because it provides hydrogen bonds to react with the PEO segments in the shell. The TSNCs exhibit a remarkable triggered size contraction and shrinkage as a result of opposing polymer thermal effects. These effects include thermal expansion of the PVA and thermal shrinkage of the F127 when the magnetic field induced a temperature change that reached 40 to 50 °C through heat generation of the magnetic nanoparticles. Depending on the PVA/F127 ratios, the TSNCs can act as a remotely triggered drug delivery platform with a tunable burst drug release profile through the structure deformation by an external magnetic field. Furthermore, the TSNCs also presented ultrasensitive magnetic resonance imaging (MRI), as demonstrated by a relatively high r 2/r 1 ratio (430). A preliminary in vivo study using the Long-Evans rat model has demonstrated a significant reduction in the spike-wave discharge after the anti-epilepsy drug, ethosuximide (ETX), was burst released from the TSNCs. These results were compared to PVA nanocarriers under the same magnetic induction as the in vitro carriers. Using a well-controlled burst release, these nanocarriers may provide significant advantages as highly temperature-responsive nanocarriers for the treatment of acute diseases.

Original languageEnglish
Pages (from-to)8566-8573
Number of pages8
JournalJournal of Materials Chemistry
Volume22
Issue number17
DOIs
StatePublished - 7 May 2012

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