Dual-Functional PEI-Poly(γ -Cholesterol-_L-Glutamate) Copolymer for Drug/Gene Co-delivery

摘要

Novel dual-functional PEI-poly(γ -cholesterol- L -glutamate) (PEI-PCHLG) copolymers are developed for the fi rst time. A series of PEI-PCHLG (PEI-1, PEI-2, PEI-3, and PEI-4) with various PEI percentages and molecular weights are successfully synthesized, among which the poor organic solvent solubility of PEI-1 precludes its further application. The other three copolymers can spontaneously self-assemble into micelles; the critical micelle concentration (CMC) values are 0.66, 1.3, and 0.95 μ mol L~(-1), respectively. PEI-2 and PEI-4, with lower CMC, are worth being further developed as promising drug carriers because of their resistance to dilution in circulation after systemic administration. However, PEI-4 can form smaller-sized micelles than PEI-2 and has similar in vitro cytotoxicity to PEI. Thus, PEI-4 is further investigated. PEI-4 micelles can not only incorporate docetaxel (DTX) with high encapsulation effi ciency (91.0) and drug loading (4.3), but also load pDNA effi ciently at a ratio of 8:1 (w/w). DTX-loaded PEI-4 micelles (DTX-PEI-4) can also carry genes with the same gene-binding capacity as PEI-4 micelles. The above three micelles (DTX-PEI-4, pDNA-PEI-4, and pDNA/DTX-PEI-4) are sub-micrometersized and spherical. The results indicate that PEI-4 containing 28.9 PEI, one of the PEI-PCHLG copoly mers, is a potential carrier for gene delivery, drug delivery, or even drug/gene co-delivery.