title: Multifunctional Polymer-Coated Carbon Nanotubes for Safe Drug Delivery.
abstract: Though progress in the use carbon nanotubes in medicine has been most encouraging for therapeutic and diagnostic applications, any translational success must involve overcoming the toxicological and surface functionalization challenges inherent in the use of such nanotubes. Ideally, a carbon nanotube-based drug delivery system would exhibit low toxicity, sustained drug release, and persist in circulation without aggregation. We report a carbon nanotube (CNT) coated with a biocompatible block-co-polymer composed of poly(lactide)-poly(ethylene glycol) (PLA-PEG) to reduce short-term and long-term toxicity, sustain drug release of paclitaxel (PTX), and prevent aggregation. The copolymer coating on the surface of CNTs significantly reducesin vitrotoxicity in human umbilical vein endothelial cells (HUVEC) and U-87 glioblastoma cells. Moreover, coating reducesin vitroinflammatory response in rat lung epithelial cells. Compared to non-coated CNTs,in vivostudies show no long-term inflammatory response with CNT coated with PLA-PEG (CLP) and the surface coating significantly decreases acute toxicity by doubling the maximum tolerated dose in mice. Using polymer coatings, we can encapsulate PTX and release over one week to increase the therapeutic efficacy compared to free drugs.In vivobiodistribution and histology studies suggests a lower degree of aggregation in tissues in that CLP accumulate more in the brain and less in the spleen than the CNT-PLA (CL) formulation.
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Moore
authors.affiliation: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, 27834, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Pitzer
authors.affiliation: Department of Physics, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Podila
authors.affiliation: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, 27834, USA.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Lewis
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Grimes
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Wilson
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Even
authors.initials: E
authors.lastname: Skjervold
authors.affiliation: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, 27834, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Brown
authors.affiliation: Department of Physics, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Apparao
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Alexis
keywords: carbon nanotubes; controlled release; drug delivery; nanomedicine; polymer coating