Rulei Yang1, Suai Zhang, Deling Kong, Xuli Gao, Yanjun Zhao, Zheng Wang. 1. Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Rd., Nankai District, Tianjin 300072, China.
Abstract
PURPOSE: To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin. METHODS: 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. RESULTS: 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). IC(50) 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. CONCLUSIONS: Micelle-forming polymer-drug conjugates containing multiple drug molecules were an efficient means to increase loading and intracellular delivery of low-potency curcumin.
PURPOSE: To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin. METHODS: 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). Humanhepatocellular carcinoma (HepG2) cells were employed to assess cytotoxicity and intracellular targeting ability of micelles. RESULTS: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). IC(50) 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. CONCLUSIONS: Micelle-forming polymer-drug conjugates containing multiple drug molecules were an efficient means to increase loading and intracellular delivery of low-potency curcumin.
Authors: Ahmad Safavy; Kevin P Raisch; Sushma Mantena; Leisa L Sanford; Simon W Sham; N Rama Krishna; James A Bonner Journal: J Med Chem Date: 2007-11-01 Impact factor: 7.446
Authors: Abhijit A Date; Mangal S Nagarsenker; Shilpa Patere; Vivek Dhawan; R P Gude; P A Hassan; V Aswal; Frank Steiniger; Jana Thamm; Alfred Fahr Journal: Mol Pharm Date: 2011-04-20 Impact factor: 4.939
Authors: Christopher D Lao; Mack T Ruffin; Daniel Normolle; Dennis D Heath; Sandra I Murray; Joanne M Bailey; Martha E Boggs; James Crowell; Cheryl L Rock; Dean E Brenner Journal: BMC Complement Altern Med Date: 2006-03-17 Impact factor: 3.659