Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide

J Pharm Sci. 2015 Nov;104(11):3851-3860. doi: 10.1002/jps.24598. Epub 2015 Jul 28.

Abstract

The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief.

Keywords: CNS; biomaterials; cell biology; cell culture; controlled release/delivery; drug interactions; drug transport; facilitated diffusion/transport; in vitro models; nanotechnology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / administration & dosage*
  • Anesthetics, Local / therapeutic use
  • Animals
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Delayed-Action Preparations / chemistry*
  • Graphite / chemistry
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / immunology
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Lidocaine / administration & dosage*
  • Lidocaine / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuralgia / drug therapy*
  • Neuralgia / immunology
  • Oxides / chemistry
  • Thalidomide / administration & dosage*
  • Thalidomide / therapeutic use

Substances

  • Anesthetics, Local
  • Cytokines
  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Oxides
  • Thalidomide
  • Graphite
  • Lidocaine