NIR Light-Triggered Quantitative Pulsed Drug Release.

Abstract

Quantitative drug release is important for improving therapeutic efficiency and avoiding side effects. While using long-term delivery system for repeated therapies, it is indispensable but challenging to accurately control the drug dosing. Here, a photocleavable prodrug loaded hydrogel is proposed for near infrared (NIR) light-triggered quantitative pulsed drug release. IR783, a commercially available NIR fluorescent dye, is conjugated with methyl honokiol (mHNK) to give a photocleavable IR783-mHNK prodrug. Injectable glycol chitosan (GC) hydrogel is chosen as a reservoir, in which IR783-mHNK can be efficiently loaded via electrostatic and hydrophobic interactions. Upon 680nm light-emitting diode (LED) light irradiation, IR783-mHNK cleaves and mHNK is released. Notably, it is found that IR783-mHNK presents synchronous photocleavage-fluorescence bleaching phenomenon. The released amount of mHNK is visible by measuring the residual fluorescent intensity of hydrogel. Quantitative drug release is achieved by controlling irradiation duration and the drug release process is visible by fluorescence imaging. The prodrug-loaded hydrogel shows good stability, minimum leakage and efficient light responsibility both in vitro and in vivo. After light triggering, monitorable quantitative mHNK release and on-demand sleep-promotiing effect are verified in mice without toxicities.