Self-assembly of pH-responsive biodegradable mixed micelles based on anionic and cationic polycarbonates for doxorubicin delivery

• Micelle is prepared by self-assembly of anionic and cationic polycarbonates.
• The ionic mixed micelle can withstand high ionic strength.
• The decrease of pH value causes the disassembly of mixed micelle.
• The micellar surface nature can be converted from negative to positive in acidic condition.
• The mixed micelle is biocompatible.

Poly(5-propyl-1,3-dioxan-2-one)-b-dimethylamine modified polycarbonate (PC(MPpC-MMA)) and poly(ethylene glycol)-b-carboxylated polycarbonate (PEG-PCCOOH) diblock copolymers were prepared to construct a pH responsive, highly stable and biodegradable mixed micelle. The two copolymers self-assembled into the mixed micelle in pH 7.4 PBS driven by electrostatic and hydrophobic interactions. PC(MPpC-MMA) with hydrophobic inner core was used for carrying drug and the dimethylamine part was designed as a trigger to disassemble the mixed micelle. PEG-PCCOOH could shield the positive character of the micelle which might show disadvantage to normal tissue. In addition, the free carboxyl groups could further increase the loading efficiency of positive charged drugs. The size and zeta potential of the micelle gradually decreased with increasing the molar ratio of PEG-PCCOOH to PC(MPpC-MMA). These mixed micelles could withstand high ionic strength of plasma and were rather stable for long time storage. However, via decrease of pH value from 7.4 to 5.0, they could undergo dissociation into smaller nanoparticles which were in a diameter of 20 nm and showed positive surface nature. In vitro drug delivery studies showed a faster release rate at pH 5.0 than that at pH 7.4. The MTT assays demonstrated potent cytotoxic activity against HepG2 cells. All these results indicate that the newly mixed polycarbonate micelle can show great potential in biomedical field.

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