Stabilization and sustained release of zeylenone, a soft cytotoxic drug, within polymeric micelles for local antitumor drug delivery.

Abstract Use of soft drugs has resulted in mixed success with the applicability to chemotherapeutics yet being confirmed. We hypothesize that incorporation of a soft cytotoxic agent into polymeric micelles, which confer to stabilizing and sustained release effect, will improve and prolong the local antitumor efficacy, thus achieving the therapeutic potential of soft cytotoxic agents. We incorporated a model soft cytotoxic agent, zeylenone, into mPEG-PLGA micelles by solvent evaporation method. The drug loaded micelles were characterized in terms of drug encapsulation, dynamic size, zeta potential, drug stability and in vitro and in vivo release. The in vivo antitumor efficacy was evaluated in A549 tumor-bearing mice. Zeylenone-loaded micelles exhibited core–shell morphology with dynamic size of about 36 nm and offered efficient solubilizing and stabilizing effects. In vitro release and in vivo pharmacokinetic results indicated sustained release of zeylenone in micelles. In addition, local delivered zeylenone-loaded micelles showed improved and sustained antitumor effect in vivo , compared with intravenous administration or local delivery of free drug solution. This study demonstrates the feasibility of soft cytotoxic agent to achieve local antitumor efficacy after the drug was stabilized and sustained the release within polymeric micelles.