title: Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics.
abstract: We report the synthesis and characterization of a polymeric nanoparticle (NP) based on hyperbranched polyglycerol (HPG) containing a hydrophobic core and a hydrophilic shell, and assessed its suitability to be developed as a systemic anticancer drug carrier. HPG NP displayed low toxicity to primary cell cultures and were well-tolerated in mice after intravenous administration. When tested in mice tumor xenograft models, HPG NP accumulated significantly in the tumors with low accumulation in the liver and the spleen. In vitro studies demonstrated that HPG NP was capable of hydrophobically binding docetaxel and releasing it in a controlled manner. The HPG NP formulation of docetaxel conferred a preferential protective effect on primary non-cancerous cells while effectively killing cancer cells, indicating great potential for widening its therapeutic index. Taken together, these data indicate that HPG NP is a highly promising nanocarrier platform for systemic delivery of anticancer drugs.
  
  
  BACKGROUND
  The use of polyethylene glycol on nano-carriers as "stealth" to deliver intravenous drugs is well known. Here, the authors developed polymeric nanoparticle (NP) with hyperbranched polyglycerol (HPG) and tested its efficacy in delivering docetaxel. The results showed that this formulation could preferentially killed cancer cells with a high therapeutic index. It seems that this platform could have a great potential in cancer therapy.
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, Canada.
authors.forename: Ripen
authors.initials: R
authors.lastname: Misri
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, Canada.
authors.forename: Nelson K Y
authors.initials: NK
authors.lastname: Wong
authors.affiliation: Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Rajesh A
authors.initials: RA
authors.lastname: Shenoi
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, Canada.
authors.forename: Christine M W
authors.initials: CM
authors.lastname: Lum
authors.affiliation: Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Chafeeva
authors.affiliation: Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Karoly
authors.initials: K
authors.lastname: Toth
authors.affiliation: Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Youcef
authors.initials: Y
authors.lastname: Rustum
authors.affiliation: Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Chemistry, University of British Columbia, Vancouver, Canada. Electronic address: jay@pathology.ubc.ca.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, Canada; Department of Surgery, University of British Columbia, Vancouver, Canada. Electronic address: MKhan4@bccancer.bc.ca.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Khan
mesh_terms: D000818:Animals; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; C043941:polyglycerol; D005990:Glycerol
keywords: Biodistribution; Docetaxel; Drug delivery; Hyperbranched polyglycerol; Nanoparticles