title: Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro.
abstract: In this study, methoxy poly(ethylene glycol)-grafted carboxymethyl chitosan (CMCPEG) was synthesized to make nanoparticles with doxorubicin (DOX) by ion complex formation. Since DOX has positive amine groups, it can interact with the carboxymethyl group of CMCPEG. The particle size of DOX-incorporated nanoparticles of CMCPEG was < 300 nm and nanoparticles had spherical shapes at morphological observation, indicating that DOX/CMCPEG mixtures can form spherical nanoparticles. In a drug release study, higher drug content induced an extended release of drug. Drug release was significantly changed by the release media pH. DOX release was faster at an acidic pH than a neutral or basic pH. The antitumor activity of DOX-incorporated nanoparticles in vitro was tested with DOX-resistant C6 glioma cells. Nanoparticles showed increased cytotoxicity compared to DOX alone. These results suggest that DOX was unable to penetrate into cells and did not effectively inhibit cell proliferation. In contrast, nanoparticles can penetrate into cells and effectively inhibit cell proliferation. Observation of cells under red fluorescence confirmed these results, i.e., nanoparticle-treated C6 cells, unlike DOX-treated cells, had strong red fluorescence. Since DOX has strong red fluorescence, DOX-incorporated nanoparticles entered into the tumor cells more than DOX alone. As a result, we suggest that DOX-incorporated nanoparticles of CMCPEG are superior candidates for antitumor drug delivery.
authors.affiliation: Department of Neurosurgery, Chonnam National University, Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Jin
authors.forename: In-Young
authors.initials: IY
authors.lastname: Kim
authors.forename: Jian
authors.initials: J
authors.lastname: Pei
authors.forename: Min
authors.initials: M
authors.lastname: Wen
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Jung
authors.forename: Kyung-Sub
authors.initials: KS
authors.lastname: Moon
authors.forename: Shin
authors.initials: S
authors.lastname: Jung
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D036103:Nanotechnology / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; C514968:carboxymethyl-chitosan; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan