title: Effects of PEGylated paclitaxel nanocrystals on breast cancer and its lung metastasis.
abstract: As an attractive strategy developed rapidly in recent years, nanocrystals are used to deliver insoluble drugs. PEGylation may further prolong the circulation time of nanoparticles and improve the therapeutic outcome of drugs. In this study, paclitaxel (PTX) nanocrystals (PTX-NCs) and PEGylated PTX nanocrystals (PEG-PTX-NCs) were prepared using antisolvent precipitation augmented by probe sonication. The characteristics and antitumor efficacy of nanocrystals were investigated. The results indicated that the nanocrystals showed rod-like morphology, and the average particle size was 240 nm and 330 nm for PTX-NCs and PEG-PTX-NCs, respectively. The PEG molecules covered the surface of nanocrystals with an 11.54 nm fixed aqueous layer thickness (FALT), much higher than that of PTX-NCs (0.2 nm). PEG-PTX-NCs showed higher stability than PTX-NCs under both storage and physiological conditions. In breast cancer xenografted mice, PEG-PTX-NCs showed significantly better tumor inhibition compared to saline (p < 0.001) and PTX-NC groups (p < 0.05) after intravenous administration. In a model of lung tumor metastasis quantified by the luciferase activity, the PEG-PTX-NCs group showed higher anticancer efficacy not only than saline and PTX-NCs groups, but also than Taxol®, achieving an 82% reduction at the end of the experiment. These studies suggested the potential advantages of PEGylated PTX nanocrystals as alternative drug delivery systems for anticancer therapy.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. wangxq@bjmu.edu.cn zqdodo@bjmu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Hu
authors.forename: Haoran
authors.initials: H
authors.lastname: Zhang
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.forename: Xinglin
authors.initials: X
authors.lastname: Wang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004058:Diffusion; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D011092:Polyethylene Glycols; D017239:Paclitaxel