title: Self-assembly of pH-responsive biodegradable mixed micelles based on anionic and cationic polycarbonates for doxorubicin delivery.
abstract: 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 20nm 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.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Lin
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, P. R. China. Electronic address: xlwang@sjtu.edu.cn.
authors.forename: Xinling
authors.initials: X
authors.lastname: Wang
mesh_terms: D000838:Anions / Q000737:chemistry*; D002412:Cations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011076:Polycarboxylate Cement / Q000737:chemistry*
chemical_list: D000838:Anions; D002412:Cations; D004337:Drug Carriers; D008823:Micelles; D011076:Polycarboxylate Cement; C005506:polycarbonate; D004317:Doxorubicin
keywords: Ionic polycarbonate; Mixed micelle; Self-assembly; pH response