The effect of hydrophilic chain length and iRGD on drug delivery from poly(ε-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles
2011
Zhu, Zhenshu | Xie, Chen | Liu, Qin | Zhen, Xu | Zheng, Xianchuang | Wu, Wei | Li, Rutian | Ding, Yin | Jiang, Xiqun | Liu, Baorui
Poly(ε-caprolactone)-b-Poly(N-vinylpyrrolidone) (PCL-b-PVP) copolymers with different PVP block length were synthesized by xanthate-mediated reverse addition fragment transfer polymerization (RAFT) and the xanthate chain transfer agent on chain end was readily translated to hydroxy or aldehyde for conjugating various functional moieties, such as fluorescent dye, biotin hydrazine and tumor homing peptide iRGD. Thus, PCL-PVP nanoparticles were prepared by these functionalized PCL-b-PVP copolymers. Furthermore, paclitaxel-loaded PCL-PVP nanoparticles with satisfactory drug loading content (15%) and encapsulation efficiency (>90%) were obtained and used in vitro and in vivo antitumor examination. It was demonstrated that the length of PVP block had a significant influence on cytotoxicity, anti-BSA adsorption, circulation time, stealth behavior, biodistribution and antitumor activity for the nanoparticles. iRGD on PCL-PVP nanoparticle surface facilitated the nanoparticles to accumulate in tumor site and enhanced their penetration in tumor tissues, both of which improved the efficacy of paclitaxel-loaded nanoparticles in impeding tumor growth and prolonging the life time of H22 tumor-bearing mice.
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