Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves neuropathic pain for eleven days

Nanomedicine. 2017 Nov;13(8):2623-2632. doi: 10.1016/j.nano.2017.07.010. Epub 2017 Jul 26.

Abstract

Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent state with a complex treatment and often poor efficacy. In this scenario, cannabinoids are increasingly regarded as a genuine alternative. In this paper, and in an experimental animal model of neuropathic pain, we studied the efficacy of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i) plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and (iii) particles possessing hydrophilic surfaces obtained by covalently binding PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug loading (13%) and small size (<300nm) with a narrow distribution and controlled surface properties (near-neutral zeta potential and stable PEG corona). Animal nociceptive behavioral studies were conducted by paw pressure and acetone tests. Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable analgesic efficacy with the longest sustained pain-relieving effect, lasting up to eleven days after one oral dose.

Keywords: Neuropathic pain; Oral administration; PLGA nanoparticles; Synthetic cannabinoid.

MeSH terms

  • Analgesics / administration & dosage*
  • Analgesics / therapeutic use
  • Animals
  • Cannabinoid Receptor Agonists / administration & dosage*
  • Cannabinoid Receptor Agonists / therapeutic use
  • Dogs
  • Drug Carriers / chemistry*
  • Lactic Acid / chemistry
  • Male
  • Nanoparticles / chemistry
  • Naphthalenes / administration & dosage*
  • Naphthalenes / therapeutic use
  • Neuralgia / drug therapy*
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Sprague-Dawley

Substances

  • Analgesics
  • Cannabinoid Receptor Agonists
  • Drug Carriers
  • Naphthalenes
  • Polyesters
  • cannabinoid receptor agonist 13
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols