title: Enhanced electrostatic interaction between chitosan-modified PLGA nanoparticle and tumor.
abstract: In our previous study, lung tumor-specific targeting of paclitaxel was achieved in mice by intravenous administration of chitosan-modified paclitaxel-loaded PLGA nanoparticles (C-NPs-paclitaxel). Transient formation of aggregates in the blood stream followed by enhanced trapping in the capillaries was proposed as a mechanism of the lung-specific accumulation of paclitaxel. In the present study, the mechanism of tumor lung preferential accumulation of paclitaxel from C-NPs-paclitaxel was investigated. Zeta potential and in vitro cellular cytotoxicity (A549 cells and CT-26 cells) of C-NPs-paclitaxel, and in vitro uptake of coumarin 6 to these cells from chitosan-modified coumarin 6 containing PLGA nanoparticles (C-NPs-coumarin 6) were examined as a function of pH (6.8, 7.4 and 8.0). The zeta potential of C-NPs-paclitaxel increased as the medium pH became more acidic. In vitro uptake of coumarin 6 by A549 cells and CT-26 cells was enhanced at lower pH for C-NPs-coumarin 6. In vitro cytotoxicity experiment with C-NPs-paclitaxel demonstrated enhanced cytotoxicity as the pH became more acidic. Therefore, enhanced electrostatic interaction between chitosan-modified PLGA nanoparticles and acidic microenvironment of tumor cells appears to be an underlying mechanism of lung tumor-specific accumulation of paclitaxel from C-NPs-paclitaxel.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Shim
authors.forename: Fu-De
authors.initials: FD
authors.lastname: Cui
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Jin
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D003374:Coumarins / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055672:Static Electricity; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D003374:Coumarins; D004337:Drug Carriers; D013844:Thiazoles; C517282:coumarin 6; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D017239:Paclitaxel