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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front. Chem. Sci. Eng.    2016, Vol. 10 Issue (3) : 348-359     DOI: 10.1007/s11705-016-1582-2
Polymeric micelle nanocarriers in cancer research
Dae Hwan Shin,Yu Tong Tam,Glen S. Kwon()
School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA
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Amphiphilic block copolymers (ABCs) assemble into a spherical nanoscopic supramolecular core/shell nanostructure termed a polymeric micelle that has been widely researched as an injectable nanocarrier for poorly water-soluble anticancer agents. The aim of this review article is to update progress in the field of drug delivery towards clinical trials, highlighting advances in polymeric micelles used for drug solubilization, reduced off-target toxicity and tumor targeting by the enhanced permeability and retention (EPR) effect. Polymeric micelles vary in stability in blood and drug release rate, and accordingly play different but key roles in drug delivery. For intravenous (IV) infusion, polymeric micelles that disassemble in blood and rapidly release poorly water-soluble anticancer agent such as paclitaxel have been used for drug solubilization, safety and the distinct possibility of toxicity reduction relative to existing solubilizing agents, e.g., Cremophor EL. Stable polymeric micelles are long-circulating in blood and reduce distribution to non-target tissue, lowering off-target toxicity. Further, they participate in the EPR effect in murine tumor models. In summary, polymeric micelles act as injectable nanocarriers for poorly water-soluble anticancer agents, achieving reduced toxicity and targeting tumors by the EPR effect.

Keywords nanomedicine      parenteral      poly(ethylene glycol)      poly(lactic acid)      reformulation     
Corresponding Authors: Glen S. Kwon   
Just Accepted Date: 08 July 2016   Online First Date: 27 July 2016    Issue Date: 23 August 2016
URL:     OR
Fig.1  Physical and chemical drug loading of polymeric micelles
Fig.2  Key steps in drug delivery via unstable and stable polymeric micelles. (A) Unstable polymeric micelle; (B) Stable polymeric micelle
Fig.3  Examples of polymeric micelles for drug solubilization
Fig.4  Rapid release of paclitaxel after IV injection of Genexol-PM® and Abraxane®
Fig.5  Schematic illustration of Triolimus
Fig.6  Schematic illustration of NK911
Fig.7  The plasma clearance of PEG5000-b-PCL5000 micelles in Balb/C mice (n = 3, SD shown as error bars) following intravenous injection at a dose of 250 mg/kg (●, concentration of copolymer above CMC upon dilution following administration) 2 mg/kg (▲, concentration of copolymer above CMC prior to administration but falls below CMC upon dilution) or 0.2 mg/kg (■, copolymer unimers). The plasma concentration data for all groups were fit using compartmental open models by Scientist software and are shown as solid lines [35]
Cyclosporin A in Cremophor EL Cyclosporin A in polymeric micelles
AUC024 /(µg?h?mL–1) 25.3±7.64 167±18.8b)
AUC0–∞ /(µg?h?mL–1) 32.7±13.8 199±20.9b)
t1/2 /h 11.5±4.58 9.40±1.20
MRT /h 14.4±6.62 9.24±2.06
CL /(L?kg–1?h–1) 0.195±0.131 0.0255±0.00319b)
Vdss /(L?kg–1) 2.33±0.785 0.232±0.0425b)
Tab.1  Non-compartmental pharmacokinetic parameters (±SD) of cyclosporin A after intravenous administration of cyclosporin A in polymeric micellar formulation in comparison to cyclosporin A in Cremophor EL (Sandimmune®) formulationa) [3]
Fig.8  Schematic illustration of NK105
Fig.9  Plasma and tumor concentrations of paclitaxel after single i.v. administration of NK105 or paclitaxel to Colon 26-bearing CDF1 mice. Plasma (A) and tumor (B) concentrations of paclitaxel after NK105 administration at a paclitaxel-equivalent dose of 50 mg/kg (●), NK105 at a paclitaxel-equivalent dose of 100 mg/kg (▲), paclitaxel 50 mg/kg (○) and paclitaxel 100 mg/kg (?) [40]
Fig.10  Schematic illustration of PEG-b-p(Asp-Hyd-DOX)
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