Injectable nanocomposite analgesic delivery system for musculoskeletal pain management

Acta Biomater. 2018 Jul 1;74:280-290. doi: 10.1016/j.actbio.2018.05.038. Epub 2018 May 25.

Abstract

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo. A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain.

Statement of significance: Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model.

Keywords: Anesthetics; Chitosan hydrogel; Injectable nanocomposite; Lipid nanocapsule; Pain management.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics* / chemistry
  • Analgesics* / pharmacokinetics
  • Analgesics* / pharmacology
  • Animals
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Dexamethasone* / chemistry
  • Dexamethasone* / pharmacokinetics
  • Dexamethasone* / pharmacology
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Drug Carriers / pharmacology
  • Female
  • Hydrogels / chemistry
  • Hydrogels / pharmacokinetics
  • Hydrogels / pharmacology
  • Male
  • Mice
  • Mice, Hairless
  • Musculoskeletal Pain* / drug therapy
  • Musculoskeletal Pain* / metabolism
  • Musculoskeletal Pain* / pathology
  • Musculoskeletal Pain* / physiopathology
  • Nanocomposites* / chemistry
  • Nanocomposites* / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Ropivacaine* / chemistry
  • Ropivacaine* / pharmacokinetics
  • Ropivacaine* / pharmacology

Substances

  • Analgesics
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Ropivacaine
  • Dexamethasone