Development of thermo-sensitive injectable hydrogel with sustained release of doxorubicin: Rheological characterization and in vivo evaluation in rats

Abstract

To develop a thermo-sensitive injectable hydrogel that is easy to administer, gels quickly in the body, and allows sustained release of the drug, various poloxamer-based hydrogels containing doxorubicin were prepared with poloxamer and hydrochloric acid under light protection using the cold method. Their rheological characterization, dissolution, and pharmacokinetics after intramuscular administration to rats were evaluated. Hydrochloric acid decreased the viscosity and retarded the gelation time of the injectable gel. The drug was dissolved from the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. P 188 and hydrochloric acid barely affected the dissolution mechanism. However, P 188 increased and hydrochloric acid decreased the dissolution rate of the drug from the injectable gels. The thermo-sensitive injectable gel composed of 0.6% doxorubicin, 15% P 407, 6% P 188, and 0.1% hydrochloric acid was easy to administer intramuscularly and gelled quickly in the body. Moreover, it maintained the plasma concentrations of drug for 60 h and gave an similar to 5-fold higher AUC compared to doxorubicin solution. Thus, it would be useful for delivering doxorubicin in a pattern that allows sustained release for a long time, leading to better bioavailability.</.