title: Polymeric nanoparticles based on chitooligosaccharide as drug carriers for co-delivery of all-trans-retinoic acid and paclitaxel.
abstract: An amphiphilic all-trans-retinoic acid (ATRA)-chitooligosaccharide (RCOS) conjugate was synthesized to form self-assembled polymeric nanoparticles to facilitate the co-delivery of ATRA and paclitaxel (PTX). The blank RCOS nanoparticles possessed low hemolytic activity and cytotoxicity, and could efficiently load PTX with a drug loading of 22.2% and a high encapsulation efficiency of 71.3%. PTX-loaded RCOS nanoparticles displayed a higher cytotoxicity to HepG2 cells compared to PTX plus ATRA solution when corrected by the accumulated drug release. Cellular uptake profiles of RCOS nanoparticles were evaluated via confocal laser scanning microscope and flow cytometry with FITC as a fluorescent mark. The RCOS nanoparticles could be rapidly and continuously taken up by HepG2 cells via endocytosis and transported into the nucleus, and the uptake rates increased with particle concentration. These results revealed the promising potential of RCOS nanoparticles as drug carriers for co-delivery of ATRA and PTX or other hydrophobic therapeutic agents.
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: jing0126@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China; Merial New Zealand, 14 blackburn road, Auckland, New Zealand. Electronic address: jian272@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: zhangxiuli2008@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: jing_jiang1974@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: xumaolei1234@163.com.
authors.forename: Maolei
authors.initials: M
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: scte@163.com.
authors.forename: Daolai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai , 264003, PR China. Electronic address: hanjingtian002@163.com.
authors.forename: Jingtian
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005453:Fluorescence; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009844:Oligosaccharides; D017239:Paclitaxel / Q000494:pharmacology*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D009844:Oligosaccharides; D011108:Polymers; C493484:oligochitosan; D002686:Chitin; D014212:Tretinoin; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel
keywords: All-trans-retinoic acid; Chitooligosaccharide; Co-delivery; Paclitaxel; Polymeric nanoparticles