title: Tuning pharmacokinetics and biodistribution of a targeted drug delivery system through incorporation of a passive targeting component.
abstract: Major challenges in the development of drug delivery systems (DDSs) have been the short half-life, poor bioavailability, insufficient accumulation and penetration of the DDSs into the tumor tissue. Understanding the pharmacokinetic (PK) parameters of the DDS is essential to overcome these challenges. Herein we investigate how surface chemistry affects the PK profile and organ distribution of a gold nanoparticle-based DDS containing both a passive and active targeting moiety via two common routes of administration: intravenous and intraperitoneal injections. Using LC/MS/MS, ELISA and INAA we report the half-life, peak plasma concentrations, area under the curve, ability to cross the peritoneal barrier and biodistribution of the nanoconjugates. The results highlight the design criteria for fine-tuning the PK parameters of a targeted drug delivery system that exploits the benefits of both active and passive targeting.
authors.affiliation: Department of Oncology Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Kudgus
authors.affiliation: Department of Oncology Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Walden
authors.affiliation: Department of Oncology Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Renee M
authors.initials: RM
authors.lastname: McGovern
authors.affiliation: Department of Oncology Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Reid
authors.affiliation: Department of Chemistry and University of Missouri Research Reactor, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.affiliation: Department of Pathology and Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma City, OK, United States of America.
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D019540:Area Under Curve; D016503:Drug Delivery Systems / Q000379:methods; D006046:Gold / Q000008:administration & dosage*; D006207:Half-Life; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D058726:Nanoconjugates / Q000008:administration & dosage*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology*
chemical_list: D058726:Nanoconjugates; D004364:Pharmaceutical Preparations; D006046:Gold