title: Biodistribution and pharmacokinetics of EGFR-targeted thiolated gelatin nanoparticles following systemic administration in pancreatic tumor-bearing mice.
abstract: The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations and higher tumor accumulations were observed with PEG-modified and EGFR-targeted nanoparticles during the study (AUClast: 17.38 and 19.56%ID/mL·h in blood, 187 and 322%ID/g·h in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as compared to control, unmodified particles (AUClast: 10.71%ID/mL·h in blood and 138%ID/g·h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor targeting efficiency than either PEG-modified or the unmodified nanoparticles, highlighting the efficacy of the active targeting strategy. In conclusion, this study shows that EGFR-targeted and PEG-modified nanoparticles were suitable vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft models.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 360 Huntington Ave, Boston, Massachusetts 02115, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Florence
authors.initials: F
authors.lastname: Gattacceca
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C572557:GE11 peptide; D007205:Indium Radioisotopes; D010455:Peptides; D011092:Polyethylene Glycols; D005780:Gelatin; C512478:EGFR protein, human; D066246:ErbB Receptors
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