Advanced applications in medicine will require well defined macromolecules capable of generating nanostructured materials with unique properties and capabilities with respect to drug delivery. Micelles are desirable as drug delivery vehicles as the hydrophobic core can incorporate hydrophobic drugs and hydrophilic shell can prolong blood circulation and improve cargo stability. Moreover, micelles below 200nm can target tumor tissue due to the enhanced permeability and retention (EPR) effect. The major obstacle of micellar drug delivery system is the lack of kinetic stability and low loading capacity. Herein, we describe novel mixed micelles formed from urea- and acid-functional polycarbonates through acid-urea hydrogen-bonding interactions to (1) address kinetic stability of micelles in ultra-dilute conditions, and (2) enhance loading levels of micelles for amphiphilic drugs. Acid- and urea-functionalized polycarbonates were synthesized via organocatalytic ring opening polymerization. Mixed micelles were formed by simply blending the acid- and urea-functional polymers prior to dissolution in water. Doxorubicin (DOX)-loading content from acid-functional micelles was found to be ~40 wt% but the particle size was found to be too large. When the mixed micelles were used, the loading was roughly the same as acid-functional micelles but with a diameter of 166 nm and narrow size distribution. In addition, the kinetic stability was significantly improved when compared to DOX-loaded acid-functional micelles. From the biodistribution studies, the DiR-loaded mixed micelles accumulated in the tumors more timely with a higher amount. DOX-loaded mixed micelles with better kinetic stability suppressed tumor growth most effectively as compared to other DOX formulations. Through TUNNEL staining, the number of apoptotic bodies in tumors treated with DOX-loaded mixed micelles was higher than that in tumors without treatment or treated with free DOX. A significantly greater number of apoptotic bodies were seen in the heart sections of mice treated with free DOX while DOX-loaded mixed micelles appear normal.

Noncovalent interaction-stabilized polymeric micelles for targeted delivery of anticancer drugs

246th National Meeting (2013)

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