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.
Highlights
Cancer remains the second most common cause of death in the US and 589,430 cancer deaths are projected to occur in 20151
DACHPt was encapsulated into DACHPt/ HANP with a high efficiency of 85 ± 5%
The physical properties of DACHPt/HANP are summarized in Intralipid Reduces Toxic Side Effects of Pt-Containing Nanodrug
Summary
Cancer remains the second most common cause of death in the US and 589,430 cancer deaths are projected to occur in 20151. Our strategy is to target the RES to temporarily blunt the uptake, i.e., to decrease the toxicities in liver and spleen and to increase the bioavailability of nanodrugs using Intralipid 20%, an FDA-approved fat emulsion used as parenteral nutrition source. The rational for this hypothesis is that the infusion of Intralipid has been reported to inhibit RES function by possibly inhibiting peritoneal clearance and impairing the phagocytic activity of Kupffer cells[29]. In rodents, Intralipid can reduce RES uptake ~50% and increase blood half-life (t1/2) ~3-fold of nano- and micron-sized superparamagnetic iron-oxide particles[31,32]
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