pH-sensitive niosomes: Effects on cytotoxicity and on inflammation and pain in murine models

J Enzyme Inhib Med Chem. 2017 Dec;32(1):538-546. doi: 10.1080/14756366.2016.1268607.

Abstract

pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In vivo antinociceptive activity (formalin test) and anti-inflammatory activity tests (paw edema induced by zymosan) in murine models were performed on drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID pharmacological activity in vivo. The synthesis of stimuli responsive surfactant, as an alternative to add pH-sensitive molecules to niosomes, could represent a promising delivery strategy for anesthetic and anti-inflammatory drugs.

Keywords: anti-nociceptive/anti-inflammatory activity; cytotoxicity; ibuprofen; lidocaine; pH-sensitive niosomes.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • BALB 3T3 Cells
  • Cells, Cultured
  • Disease Models, Animal*
  • Fibroblasts / drug effects
  • Humans
  • Hydrogen-Ion Concentration
  • Ibuprofen / administration & dosage
  • Ibuprofen / pharmacology*
  • Inflammation / drug therapy*
  • Lidocaine / administration & dosage
  • Lidocaine / pharmacology*
  • Liposomes / administration & dosage
  • Liposomes / chemistry*
  • Liposomes / pharmacology
  • Mice
  • Pain / drug therapy*
  • Pain Measurement
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Liposomes
  • Surface-Active Agents
  • Lidocaine
  • Ibuprofen