title: Biotinylated PAMAM dendrimers for intracellular delivery of cisplatin to ovarian cancer: role of SMVT.
abstract: OBJECTIVE
  The aim of this study was to prepare biotinylated PAMAM dendrimers loaded with cisplatin and to evaluate the cytotoxicity in ovarian cancer cell lines.
  
  
  METHODS
  Biotinylated and unconjugated dendrimer-cisplatin complexes were investigated for encapsulation efficiency, in vitro cytotoxic activity and cellular accumulation of cisplatin in OVCAR-3, SKOV-3, A2780 (wild-type) and CP70 (A2780/CP70, cisplatin-resistant) cells.
  
  
  RESULTS
  Encapsulation efficiency of cisplatin ranged from 5.33% to 21.10%. In vitro cytotoxic activity revealed that IC(50) values of dendrimer-cisplatin complexes were significantly lower than that of free cisplatin in OVCAR-3, SKOV-3 and CP70 cell lines. Cellular uptake data showed highest accumulation of platinum by PAMAMG(4) NH(2) dendrimer complexes of cisplatin in A2780 (19.41±0.85 μg/ml) and CP70 (25.25±1.25 μg/ml) cell lines in comparison with cisplatin uptake of only 1.77±0.351 μg/ml in A2780 and 2.31±0.421 μg/ml in CP70 cells.
  
  
  CONCLUSIONS
  In conclusion, biotinylated PAMAM dendrimers may be utilized as potential targeting agents for cisplatin delivery to ovarian cancer.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, 1010 W Ave B, Kingsville, TX, 78363, USA. palakurthi@pharmacy.tamhsc.edu
authors.forename: Venkata K
authors.initials: VK
authors.lastname: Yellepeddi
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Vangara
authors.forename: Srinath
authors.initials: S
authors.lastname: Palakurthi
mesh_terms: D019921:Biotinylation / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D050091:Dendrimers / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008422:Materials Testing; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D027981:Symporters; C119981:biotin transporter; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin