A thermoresponsive hydrophobically modified hydroxypropylmethylcellulose/cyclodextrin injectable hydrogel for the sustained release of drugs

Abstract

The objective of this study was to develop a thermoresponsive injectable hydrogel for the sustained release of drugs by taking advantage of host-guest interactions between a hydrophobically modified hydroxypropylmethyl cellulose (HM-HPMC) and cyclodextrin (CD). A thermoresponsive injectable hydrogel was prepared by simply adding CDs to HM-HPMC hydrogel. The HM-HPMC hydrogel was converted into a sol with a low viscosity through host-guest interactions with CDs. The HM-HPMC/β-CD hydrogel became a gel near body temperature where the host dissociated from the hydrophobic moieties of the polymer in response to the temperature. The yield stress of the HM-HPMC became progressively lower on the addition of β-CD which was desirable in the case of developing an injectable formulation. When the HM-HPMC/β-CD hydrogel containing indocyanine green (ICG) was subcutaneously administered to mice, the fluorescence of the ICG remained relatively constant for 24h after the administration, which was substantially longer than that for ICG alone or an HPMC formulation. The plasma insulin level was maintained for a longer period of time when the HM-HPMC/β-CD containing insulin was administered and the MRT value was increased by 1.6 times compared to a solution of insulin alone. In addition, the HM-HPMC/β-CD hydrogel formulation showed a prolonged hypoglycemic effect in response to the insulin which was slowly released from the hydrogel. A thermoresponsive injectable hydrogel was successfully constructed from the highly viscous HM-HPMC and β-CD, and the resulting formulation functioned as a sustained release carrier for drugs.