title: Targeted paclitaxel delivery to tumors using cleavable PEG-conjugated solid lipid nanoparticles.
abstract: OBJECTIVE
  To develop a tumor-targeted drug delivery system based on solid lipid nanoparticles (SLNs) conjugated with the enzymatically cleavable polyethylene glycol (PEG).
  
  
  METHODS
  SLNs loaded with paclitaxel (PTX) were prepared using the film ultrasonication method, followed by conjugation with a PEGylated peptide (Pp) that can specifically interact with matrix metalloproteinases (MMPs) that is over-expressed by tumor cells. The physicochemical characteristics of the Pp-PTX-SLNs were studied and the in vitro drug release, cytotoxicity and cell uptake of the formulations were investigated. Furthermore, using an animal model, the pharmacokinetic properties, biodistribution and anti-tumor activity of this system were evaluated.
  
  
  RESULTS
  The resulting Pp-PTX-SLNs penetrated through tumor cells via facilitated uptake mediated by MMPs. The uncleavable Pp'-PTX-SLNs showed a lower cell uptake efficiency, compared with the Pp-PTX-SLNs. In a tumor-bearing mice model, Pp-PTX-SLNs accumulated to a greater extent at the tumor location, persisted longer in blood circulation, and showed lower toxicity than did PTX-SLNs or Taxol®. Most importantly, the mice treated with Pp-PTX-SLNs survived longer than the groups treated with Pp'-PTX-SLNs, PTX-SLNs or Taxol®.
  
  
  CONCLUSIONS
  These results suggest that Pp-PTX-SLNs hold promise as a new strategy for paclitaxel chemotherapy, and that Pp-SLNs can be a useful nanocarrier for other chemotherapeutic drugs.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.forename: Abdelbary
authors.initials: A
authors.lastname: Elhissi
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D016466:CHO Cells; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008055:Lipids; D010446:Peptide Fragments; D011092:Polyethylene Glycols; D017239:Paclitaxel