In vivo efficacy of paclitaxel-loaded injectable in situ-forming gel against subcutaneous tumor growth

Abstract

Injectable in situ-forming gels have received considerable attention as localized drug delivery systems. Here, we examined a poly(ethylene glycol)-b-polycaprolactone (MPEG-PCL) diblock copolymer gel as an injectable drug depot for paclitaxel (Ptx). The copolymer solution remained liquid at room temperature and rapidly gelled in vivo at body temperature. In vitro experiments showed that Ptx was released from MPEG-PCL copolymer gels over the course of more than 14 days. Experiments employing intratumoral injection of saline (control), gel-only, Taxol, or Ptx-loaded gel into mice bearing B16F10 tumor xenografts showed that Ptx-loaded gel inhibited the growth of B16F10 tumors more effectively than did saline or gel alone. Further, intratumoral injection of Ptx-loaded gel was more efficacious in inhibiting the growth of B16F10 tumor over 10 days than was injection of Taxol. A histological analysis demonstrated an increase in necrotic tissue in tumors treated with Ptx-loaded gel. In conclusion, our data show that intratumoral injection of Ptx-loaded MPEG-PCL diblock copolymer yielded an in situ-forming gel that exhibited controlled Ptx release profile, and that was effective in treating localized solid tumors. © 2010 Elsevier B.V.