Abstract
A dilemma for current cancer therapy is surgical injury in addition to the toxicities and inefficiencies of systemic chemotherapy. Meanwhile, localized therapies have become a noticeable strategy. In this study, Cucurbitacin (Cuc)-loaded poly(lactic-co-glycolic acid) particles of different sizes (about 50 μm, 5 μm, and 270 nm, respectively) were prepared as the sustained-release system for intratumoral injection, and their physicochemical properties, in vitro cytotoxicity, particles-cells interactions, pharmacokinetics, and pharmacodynamics were systemically investigated for the first time. The results of cytotoxicity experiments and pharmacokinetic/pharmacodynamic studies indicated that the release patterns of the particles would strongly affect the biological efficiency not only at the cell level but also in two types of animal models. Cuc raw material and nanoparticles showed higher initial burst release in vitro, and higher drug concentration in tumor and plasma. Large particles (about 50 μm) showed lower initial burst and slow drug release, which would not supply enough amount of drug to inhibit the cancer cell growth during the whole treatment period. Particles with mean diameter of about 5 μm performed the best anti-melanoma efficiency both in vitro and in vivo. The release patterns, instead of the particles-cells interactions, would be the key factors to affect the biological effects of the particulate system for intratumoral injection.
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