Naproxen sodium nanoparticles are less toxic and gastroprotective agents than the conventional NSAID drug naproxen sodium in Balb/c mice

Toxicol Appl Pharmacol. 2022 Oct 1:452:116192. doi: 10.1016/j.taap.2022.116192. Epub 2022 Aug 8.

Abstract

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of gastric ulcers. Excellent therapeutic properties have made the use of NSAIDs widespread. Nano-drug delivery to reduce systemic toxicity through modulating drug pharmacokinetics may be a better choice. Presently, we investigated if naproxen nanoformulation (PVA capped NPRS-MgO NPs) is less toxic to be used as an alternative drug. Groups of mice were assigned to control, NPRS-treated, CNF-treated, UNF-treated, and MgO NPs-treated groups. Analyses included gross examination of gastric mucosa, calculation of ulcer and inhibition indices, determination of tissue levels of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and reduced glutathione (GSH), histological and immunohistochemical assessment of i-NOS, COX-2, and caspase-3 of stomach mucosa, q-PCR for the detection of mRNA expression of IL-1β, IL-6, and TNF-α. Results were compared statistically at P < 0.05. Compared to NPRS-treated mice which developed multiple ulcers, had elevated MDA and ROS levels, and deceased CAT, POD, SOD, and GSH levels, significantly increased expression of IL-1β, IL-6, and TNF-α mRNA, damaged surface epithelium with disrupted glandular architecture and leucocyte infiltration of lamina propria with a marked increase in mucosal COX-2, i-NOS, and caspase-3 expression, oral administration of coated and uncoated naproxen nanoformulations prevented the gross mucosal damage by a restoration of all biochemical, histological, and immunohistochemical alterations to near control levels. The present study demonstrates that naproxen sodium nanoformulation has a gastroprotective action and in the clinical setting can be a better alternative to conventional naproxen.

Keywords: Antioxidant enzymes; Drug-loaded nanoparticles; IL-1ꞵ; IL-6; NPRS-induced gastric ulcer; TNF-α; iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Interleukin-6 / metabolism
  • Magnesium Oxide / metabolism
  • Magnesium Oxide / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / therapeutic use
  • Naproxen / metabolism
  • Naproxen / pharmacology
  • Naproxen / therapeutic use
  • Pharmaceutical Preparations / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Stomach Ulcer* / prevention & control
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Pharmaceutical Preparations
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Magnesium Oxide
  • Naproxen
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Caspase 3