Pharmaceutical Research

, Volume 29, Issue 12, pp 3512–3525 | Cite as

Biodegradable Polymer-Curcumin Conjugate Micelles Enhance the Loading and Delivery of Low-Potency Curcumin

Research Paper



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.


curcumin drug loading micelle mPEG-PLA polymer-drug conjugate 



confocal laser scanning microscope


critical micelle concentration




mono-carboxyl-terminated curcumin




4-dimethylamino pyridine


Dulbecco’s modification of eagle’s medium




enhanced permeability and retention effect


gluraric anhydride


generally regarded as safe


human hepatocellular carcinoma cells


high performance liquid chromatography


methoxy-poly(ethylene glycol)


mononuclear phagocyte system


molecular weight cut-off


N-hydroxy succinimide


nuclear magnetic resonance




poly(lactic acid)


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.

Supplementary material

11095_2012_848_MOESM1_ESM.tif (3.9 mb)
Esm 1 1H NMR spectra of mPEG-PLA, mPEG-PLA-COOH, and mPEG-PLA-Tris. (TIFF 4019 kb)
11095_2012_848_MOESM2_ESM.tif (184 kb)
Esm 2 1H NMR spectra of Cur-GA, 821. (TIFF 183 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency School of Pharmaceutical Science & TechnologyTianjin UniversityTianjinChina
  2. 2.Institute of Biomedical EngineeringChinese Academy of Medical Sciences Peking Union Medical CollegeTianjinChina
  3. 3.Key Laboratory of Bioactive Materials, Ministry of Education, College of Life ScienceNankai UniversityTianjinChina

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