Etoposide is widely used in the
chemotherapy of a variety of
malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of
etoposide limit its clinical application. The aim of this study was to develop sustained-release
etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing
etoposide, poly(L-lactid
acid) and
polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-
excipient compatibility, content uniformity, morphology,
sterility, in vitro, and in vivo release profiles. Then the antitumor activity of the implants was tested in xenograft model of A549 human
non-small cell lung cancer. SEM images displayed smooth surface of the implant and indicated that
etoposide was homogeneously dispersed in the polymeric matrix. The results of content uniformity met the requirements of the Chinese Pharmacopoeia. Both in vitro and in vivo release profiles of the implants were characterized by high burst release followed by sustained release of
etoposide. Intratumoral implantation of
etoposide-loaded implants could efficiently delay the
tumor growth. Furthermore, increasing the dose of implants led to higher
tumor suppression rate without adding systemic toxicity. These results indicated that
etoposide-loaded implants have significant antitumor efficacy in xenograft model without dose-limiting side effects and they possess a strong potential to be used as an intratumoral
chemotherapy option for
lung cancer treatment.