title: Impact of surfactant treatment of paclitaxel nanocrystals on biodistribution and tumor accumulation in tumor-bearing mice.
abstract: We have previously tested paclitaxel nanocrystals (PTX-NCs) in tumor murine models and learned that the nanocrystal formulation could achieve similar and superior anticancer efficacy to the conventional Taxol® formulation, but with significantly reduced side-effects. The nanocrystals were not coated with any surfactants and a majority of the injected dose was taken up by the liver (>40%), while a minimal amount was present in the blood circulation and quickly eliminated. The aim of this work was to treat the surface of PTX-NCs with PEG-based polymers and examine the impact by surface coating on biodistribution, pharmacokinetics, and tumor retention. Testing in tumor-bearing mice showed that PTX-NCs treated with Pluronic® F68 (PEG-PPG-PEG block polymer) significantly enhanced blood circulation of the drug and accumulation in tumor tissue. The absolute amount reaching the tumor, however, was still minimal relative to the dose.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United States; School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United States. Electronic address: tonglei@purdue.edu.
authors.forename: Tonglei
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011409:Propylene Glycols; D013501:Surface-Active Agents; C528875:poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer; D020442:Poloxamer; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Biodistribution; Nanocrystals; PEG; Paclitaxel; Surfactant; Tumor