A novel, thermosensitive
hydrogel,
poly(organophosphazene), is an
injectable drug delivery system that transforms from
sol to gel at body temperature.
Doxorubicin (DOX) is a cytotoxic
drug used for the treatment of several solid
tumors. Due to its acute
cardiac toxicity, DOX is a good candidate for local chemo-drug delivery system. In this study, we evaluated the pharmacokinetics of DOX (30 mg/kg) when given as an intratumoral injection using
poly(organophosphazene)
hydrogel in mice with human gastric
tumor xenografts. DOX was formulated at 0.6% into
a 10%
hydrogel, and 40% and 90% of the dose was released in a sustained manner over 5 weeks in vitro and in vivo, respectively. The
hydrogel mass was well retained over 7 weeks, and T(1/2beta,
tumor) was 1.8-fold longer than that of the
solution, but the 2.2-fold lower C(max,
tumor), produced a similar AUC(
tumor) and antitumor effect. However,
solution caused a 2-fold higher systemic exposure (AUC(plasma)), which resulted in significant mortality due to acute
cardiac toxicity. These data indicate that
hydrogel formulation may have similar efficacy but lower systemic exposure than aqueous
solution. In conclusion,
poly(organophosphazene) showed adequate characteristics for local intratumoral delivery of DOX, including dose capacity, local retention, and minimal systemic spill-over. The safety and biocompatibility of
poly(organophosphazene) should be further evaluated and its application should be extended to other
anticancer agents.