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

• Published in: Macromolecular chemistry and physics 2014-01, Vol.215 (2), p.163-170
• Main Authors: Zhang, Jinkun, Fang, Dailong, Ma, Qing, He, Zhiyao, Ren, Ke, Zhou, Rui, Zeng, Shi, Li, Bo, He, Lili, He, Gu, Song, Xiangrong
• Format: Article
• Language: English
• Subjects: Aminoacid polymers; Applied sciences; Biological and medical sciences; co-delivery; copolymers; Exact sciences and technology; General pharmacology; Medical sciences; micelles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; poly(ethylene imine); Synthetic biopolymers
• ISSN: 1022-1352; 1521-3935
• DOI: 10.1002/macp.201300551

Novel dual‐functional PEI‐poly(γ‐cholesterol‐l‐glutamate) (PEI‐PCHLG) copolymers are developed for the first 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 μmol 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 efficiency (91.0%) and drug loading (4.3%), but also load pDNA efficiently 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‐micrometer‐sized and spherical. The results indicate that PEI‐4 containing 28.9% PEI, one of the PEI‐PCHLG copoly­mers, is a potential carrier for gene delivery, drug delivery, or even drug/gene co‐delivery. A series of novel amphiphilic PEI‐poly(γ‐cholesterol‐L‐glutamate) (PEI‐PCHLG) copolymers are synthesized and characterized. One of PEI‐PCHLG copolymers can self‐assemble into micelles. The PCHLG block assembles into micelles with high drug entrapment, and the grafted PEI block can act as a hydrophilic section exposed outside the micelles, which are capable of carrying genes. Thus PEI‐PCLG copolymers are potential carriers for drug/gene co‐delivery.