title: Hyaluronic acid-decorated PLGA-PEG nanoparticles for targeted delivery of SN-38 to ovarian cancer.
abstract: BACKGROUND
  Extreme hydrophobicity and poor stability of SN-38, a highly potent topoisomerase I inhibitor, has prevented its clinical use. Its encapsulation into nanoparticles may be a way to overcome these problems. Here we report the use of SN-38-loaded hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) for targeted ovarian cancer therapy.
  
  
  METHODS
  PLGA-PEG nanoparticles loaded with SN-38 were prepared by single- emulsion (O/W) solvent evaporation method. HA was decorated onto the nanoparticles by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) coupling and the extent of HA conjugation was quantified by hexadecyltrimmethylammonium bromide (CTAB) assay. Cancer cell specificity of the NPs was determined by flow cytometry and cytotoxicity of the NPs was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium (MTT) bromide assay.
  
  
  RESULTS
  Mean size, zeta potential and encapsulation efficiency of PLGA-PEG-HA NPs were 265.6 ± 3.8 nm, -30.4 ± 0.1 mV and 75.8 ± 4.1%, respectively. Cellular uptake of PLGA-PEG-HA NPs was 8- and 16-fold higher in CD44-positive cell lines, SKOV-3 and OVCAR-8, as compared to CD44-negative cells (CHO). Cytotoxicity of the targeted NPs was significantly higher as compared to non-targeted NPs for the above cell lines. These results suggest that PLGA-PEG-HA NPs could be an efficient delivery system for SN-38 for targeted therapy of ovarian cancer.
authors.affiliation: Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Vangara
authors.forename: Jingbo Louise
authors.initials: JL
authors.lastname: Liu
authors.forename: Srinath
authors.initials: S
authors.lastname: Palakurthi
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006224:Cricetinae; D004337:Drug Carriers; D004655:Emulsions; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D000077146:Irinotecan; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D011098:Polyglactin 910 / Q000737:chemistry / Q000627:therapeutic use*; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D018960:Hyaluronan Receptors; D059004:Topoisomerase I Inhibitors; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D000077146:Irinotecan; D006820:Hyaluronic Acid; D002166:Camptothecin
keywords: CD44-targeted delivery; CTAB assay; PLGA nanoparticles; SN-38; hyaluronic acid; ovarian cancer; surface decoration