title: Deoxycholic acid-modified chitooligosaccharide/mPEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy.
abstract: Poly(ethylene glycol) (PEG) as a block in polymeric micelles can prolong circulation life and reduce systemic clearance but decrease the cellular uptake. To overcome this limitation, a mixed micelle composed of deoxycholic acid-modified chitooligosaccharide (COS-DOCA) and methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA) was designed to load paclitaxel (PTX). The PTX-loaded mixed micelles was prepared by nanoprecipitation method with high drug-loading efficiency of 8.03% and encapsulation efficiency of 97.09% as well as small size (∼40 nm) and narrow size distribution. COS-DOCA/mPEG-PDLLA mixed micelles exhibited the sustained release property. Due to the positive charge and bioadhesive property of COS-DOCA, the cellular uptake of PTX in mixed micelles was higher in cancer cells but lower in macrophage cells compared to the mPEG-PDLLA micelles. The systemic toxicity of PTX in mixed micelles was much lower than Taxol using zebrafish as a toxicological model. Furthermore, the PTX-loaded COS-DOCA/mPEG-PDLLA mixed micelles can prolong the blood circulation time of PTX and enhance the antitumor efficacy in A549 lung xenograft model. Our findings indicate that COS-DOCA/mPEG-PDLLA mixed micelles could be a potential vehicle for enhanced delivery of anticancer drugs.
authors.affiliation: Department of Chemical and Biological Engineering, Zhejiang University of Science & Technology, Hangzhou, Zhejiang, PR China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Jiang
authors.affiliation: First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China. Electronic address: wanghx@zju.edu.cn.
authors.forename: Hangxiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Hangzhou PushiKang Biotechnology Co., Ltd., Zhejiang, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hangzhou PushiKang Biotechnology Co., Ltd., Zhejiang, PR China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: College of Life and Environmental Science, Shanghai Normal University, Shanghai, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Hangzhou PushiKang Biotechnology Co., Ltd., Zhejiang, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002686:Chitin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003840:Deoxycholic Acid / Q000009:adverse effects / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D009844:Oligosaccharides / Q000009:adverse effects / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013499:Surface Properties; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D009844:Oligosaccharides; D011091:Polyesters; C561465:methoxy poly(ethylene glycol)-block-poly(lactic acid); C493484:oligochitosan; D003840:Deoxycholic Acid; D002686:Chitin; D011092:Polyethylene Glycols; D048271:Chitosan; D017239:Paclitaxel
keywords: Chitooligosaccharide; Mixed micelles; PEG-PDLLA; Paclitaxel; Polymeric micelles