title: Development and characterization of stabilized double loaded mPEG-PDLLA micelles for simultaneous delivery of paclitaxel and docetaxel.
abstract: OBJECTIVE
  Double loaded micelles (DLM) in which paclitaxel (PTX) and docetaxel (DTX) were co-solubilized with monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PLA) copolymer were prepared and evaluated in an aim to investigate the effect of a combination of PTX and DTX on the stability of mPEG-PLA micelles compared to single drug-loaded micelles (SDM), especially that recent clinical anticancer formulations are limited by the existence of toxic excipients and stability issues.
  
  
  METHODS
  The SDM and DLM of PTX and DTX were prepared by a solvent evaporation method. Micellar size, size distribution, drug loading content and drug release were investigated. Transmission electron microscopy was used to investigate the stabilization mechanism.
  
  
  RESULTS
  The drug loading efficiency of both PTX and DTX in DLM and SDM were 25% and 10%, respectively. (1)H NMR showed a successful encapsulation of both drugs in the polymeric micelle. DLM showed better physical stability at drug concentrations higher than 1 mg/mL compared to SDM. Moreover, DLM, SDM-PTX and SDM-DTX were stable for 24, 9 and 1 h, respectively. The stabilization mechanism of DLM was investigated, a network structure of DLM was observed in TEM graphs. Furthermore, DLM showed complete and faster drug release compared to SDM. mPEG-PLA double loaded micelles can deliver two poorly water soluble anticancer drugs at clinically relevant doses. The obtained results offer a promising alternative for double drug therapy without any formulation associated undesirable effects and encourage further in vivo development and optimization of the DLM as a drug delivery system for anticancer drugs.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University , Nanjing , China and.
authors.forename: Ammar
authors.initials: A
authors.lastname: Ouahab
authors.forename: Chengyi
authors.initials: C
authors.lastname: Shao
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D015195:Drug Design; D065546:Drug Liberation; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; C492425:methoxy poly(ethylene glycol)-poly(lactide); D000077143:Docetaxel; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Double loaded micelles; in vitro drug release; micelle stability; polymeric micelles; taxanes