title: A new approach to reduce toxicities and to improve bioavailabilities of platinum-containing anti-cancer nanodrugs.
abstract: Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Maggie
authors.initials: M
authors.lastname: Lu
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Wei
authors.affiliation: Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Shen-Chuan
authors.initials: SC
authors.lastname: Lo
authors.affiliation: Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Shian-Jy
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bain
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA.
authors.forename: Chien
authors.initials: C
authors.lastname: Ho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D006820:Hyaluronic Acid / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010984:Platinum / Q000493:pharmacokinetics* / Q000633:toxicity*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000068936:Theranostic Nanomedicine
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D010984:Platinum; D006820:Hyaluronic Acid