title: Biodegradable polymer-curcumin conjugate micelles enhance the loading and delivery of low-potency curcumin.
abstract: OBJECTIVE
  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.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Rd., Nankai District, Tianjin 300072, China.
authors.forename: Rulei
authors.initials: R
authors.lastname: Yang
authors.forename: Suai
authors.initials: S
authors.lastname: Zhang
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.forename: Xuli
authors.initials: X
authors.lastname: Gao
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D003474:Curcumin