Synthesis of low-molecular-weight gel with tunable gel-sol transition temperature for thermo-sensitive drug controlled release

Abstract

A phenylboronic acid (PBA)-based gelator was synthesized, and host-guest low-molecular-weight gel (LMWG) was fabricated by the inclusion complexes (ICs) of the gelator and β-cyclodextrin (β-CD). Translucent gel consisting of nanofiber or nanobelt (60–430 nm wide) was obtained with low critical gelation concentration (CGC) of 2.9 mg/mL (0.36 wt%). The gel-sol transition temperature (Tgel) of the IC gel could be regulated from 37.5 °C to 44.9 °C by different inclusion ratio of gelator and β-CD. And the rheological properties exhibited the rapid recovery of the sol, the gel was re-formed in 2.5 min at 37 °C, and fully restored the initial storage modulus (G’). This tunable gel-sol-gel transition has been applied in thermo-sensitive controlled release of naproxen for tumor fever. Naproxen (16.7 μg•mL−1•min−1) was released from the drug-loaded gel (Loading Efficiency = 8.3%) when heated at 38.5 °C, and the release process terminated when the sol reconverted into gel at 37 °C, and it was achieved again when the gel converted to sol at 38.5 °C. Both the blank and drug-loaded gel could gellated rapidly after subcutaneous injection. The stability of gel was greatly improved to 102 h by the salts' induce, and the gel-sol transition was also controlled by vary kinds of salts and salt concentration.