Stimuli-Responsive Nanocapsules for the Spatiotemporal Release of Melatonin: Protection against Gastric Inflammation

Sumit Kumar Pramanik, Uttam Pal, Preety Choudhary, Harwinder Singh, Russel J. Reiter, Anitha Ethirajan, Snehasikta Swarnakar, Amitava Das

Research output: Contribution to journalArticle

Abstract

Melatonin is a secretory product of the pineal gland that regulates circadian rhythm. It is also well-known for its anti-inflammatory and antioxidant properties against the damaging influences of reactive oxygen species. To improve its therapeutic efficacy, a new formulation with melatonin loaded in a stimuli-responsive polymeric nanocapsule has been prepared following an inverse mini-emulsion technique. The colloidal stability of the melatonin-loaded nanocapsules (MNCs) is studied using dynamic light scattering, while the morphology of these MNCs is characterized using various electron microscopies. These MNCs have an inner diameter of 80-120 nm with a cell wall thickness of 29 ± 11 nm. The emission band maximum for melatonin appears at 350 nm following excitation at 305 nm (quantum yield, φ350 = 0.13). The self-quenching nature of the entrapped melatonin molecules inside the nanocapsules attributes to a lower φ350 value for the MNCs. The controlled release of melatonin from MNCs in an in vitro condition is achieved by inducing a rupture of the polymeric backbone through maintaining a certain media pH (∼2.0-4.0) as an external stimulus, and this accounts for a significant enhancement in its characteristic luminescence. The H,K-ATPase, an integral membrane protein, maintains this specific pH range in the interior of the gastrointestinal tract. This methodology is adopted for developing an efficient drug delivery process in the gastric environment. A significant improvement in the AGS cell survival under oxidative stress conditions is observed during preincubation with MNCs compared to free melatonin. In a murine model of the stress-induced gastric ulcer, MNCs outperformed free melatonin in terms of drug efficacy. The value for the gastric ulcer index is reduced from ∼30 to ∼15 by free melatonin and from ∼30 to ∼8 by MNCs treatments, respectively. Such formulation could be a step forward for developing more efficient melatonin-based gastroprotective supplements.

Original languageEnglish (US)
Pages (from-to)5218-5226
Number of pages9
JournalACS Applied Bio Materials
Volume2
Issue number12
DOIs
StatePublished - Dec 16 2019

Keywords

  • animal model
  • drug release
  • gastric ulcer
  • melatonin
  • nanocapsules
  • pH-responsive
  • targeted delivery

ASJC Scopus subject areas

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

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