Biodegradable Polymer-Curcumin Conjugate Micelles Enhance the Loading and Delivery of Low-Potency Curcumin
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To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin.
Multiple curcumin molecules were conjugated to poly(lactic acid) (PLA) via tris(hydroxymethyl)aminomethane (Tris) linker producing the hydrophobic drug-binding block; methoxy-poly(ethylene glycol) (mPEG) was employed as the hydrophilic block. Micelles were characterized by size, loading capacity, stability, and critical micelle concentration (CMC). Human hepatocellular carcinoma (HepG2) cells were employed to assess cytotoxicity and intracellular targeting ability of micelles.
mPEG-PLA-Tris-Cur micelles were within nanorange (<100 nm). CMC of such micelles (2.3 ± 0.4 μg/mL) was 10 times lower than mPEG-PLA micelles (27.4 ± 0.8 μg/mL). Curcumin loading in mPEG-PLA-Tris-Cur micelles reached 18.5 ± 1.3% (w/w), compared to traditional mPEG-PLA micelles at 3.6 ± 0.4% (w/w). IC50 of mPEG-PLA-Tris-Cur micelles (~22 μg/mL at curcumin-equivalent dose) was similar to unmodified curcumin. Placebo and drug-encapsulated conjugate micelles could be efficiently internalized to cytoplasmic compartment of HepG2 cells.
Micelle-forming polymer-drug conjugates containing multiple drug molecules were an efficient means to increase loading and intracellular delivery of low-potency curcumin.
KEY WORDScurcumin drug loading micelle mPEG-PLA polymer-drug conjugate
confocal laser scanning microscope
critical micelle concentration
Dulbecco’s modification of eagle’s medium
enhanced permeability and retention effect
generally regarded as safe
human hepatocellular carcinoma cells
high performance liquid chromatography
mononuclear phagocyte system
molecular weight cut-off
nuclear magnetic resonance
red blood cells
Acknowledgments and Disclosures
This work was supported by Tianjin Research Program of Application Foundation and Advanced Technology (11JCZDJC20600; 11JCYBJC10300), National Natural Science Foundation of China (81171478; 31100699), and the Research Fund for the Doctoral Program of Higher Education of China (20110032120077).
The authors of this article have no conflicts of interest to declare.
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