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The Anti-Melanoma Efficiency of the Intratumoral Injection of Cucurbitacin-Loaded Sustained Release Carriers: In Situ-Forming Implants

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Abstract

Our previous studies revealed that the PLGA-based particulate systems loaded with cucurbitacin showed limited anti-melanoma efficiency in xenograft animal models after intratumoral injection, which was due to the undesirable initial burst release and the leakage of the particulate carriers from the injection site through the pinhole. In this paper, two categories of in situ-forming implants (ISFIs) for intratumoral injection, PLGA ISFIs and SAIB ISFIs, were systemically evaluated for their potentials for on solid tumor treatment via intratumoral injection. The in vitro drug release profiles of these two ISFIs were different due to the different sol–gel transition properties. The pharmacodynamics results revealed that SAIB ISFIs displayed obvious therapeutic efficiencies to melanoma, and multi-points injection of SASIB ISFIs displayed better efficiency than single-point injection. The different sol–gel transition properties and mechanism for PLGA ISFIs and SAIB ISFIs affected both the drug release and strongly impacted the pharmacokinetic parameters and pharmacodynamic effectiveness. Also, the adhesive property of SAIB to the local tissue could extend the retention and inhibit the leakage of the SAIB ISFIs, thus enhanced the anticancer effectiveness. Comparison of the various intratumoral injection systems, appropriate drug release profiles (lower initial burst and steady release) and good retention (minimum leakage from the injection site) would benefit to the antitumor effects of the intratumoral depots.

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Acknowledgments

We thank Prof. Deng Yihui, Shenyang Pharmaceutical University, for his helpful comments on animal studies, Mr. Tian Han, Zhongshan School of Medicine, SUN YAT-SEN University, for his help on cellular experiments and results explanations, and Prof. Takshi Ikejima, Shenyang Pharmaceutical University, who kindly provided the A375.S2 human melanoma cell.

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Correspondence to Hui Xu.

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Guo, J., Wang, J., Cai, C. et al. The Anti-Melanoma Efficiency of the Intratumoral Injection of Cucurbitacin-Loaded Sustained Release Carriers: In Situ-Forming Implants. AAPS PharmSciTech 16, 973–985 (2015) doi:10.1208/s12249-015-0292-2

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KEY WORDS

  • anti-melanoma efficiency
  • cucurbitacin
  • drug release
  • in situ-forming implants (ISFIs)
  • intratumoral injection