# Ammonia-triggered disintegration of kappa-carrageenan hydrogel carrier for site-specific anti-inflammatory drug delivery

## TL;DR

This paper introduces a smart hydrogel that releases anti-inflammatory drugs in ammonia-rich environments, offering a targeted treatment for ammonia-induced inflammation.

## Contribution

The novelty lies in the development of a kappa-carrageenan-based hydrogel that selectively responds to ammonia for site-specific drug delivery.

## Key findings

- Exposure to ammonium hydroxide caused structural disruption of the hydrogel and accelerated drug release.
- Celecoxib release reached 86% in ammonia-rich conditions versus 33% under normal conditions.
- The formulation showed enhanced anti-inflammatory effects and a favorable safety profile in cell-line assays.

## Abstract

Ammonia accumulation in tissues is increasingly recognized as a direct biochemical trigger of ammonia-induced inflammation, yet no therapeutic strategy currently exists that can selectively target this pathological condition while minimizing systemic toxicity. Addressing this critical gap, the present study introduces a first-of-its-kind kappa-carrageenan (KC)-based formulation engineered to respond selectively to ammonia-rich inflammatory environments while simultaneously exerting synergistic anti-inflammatory effects. The KC gel’s structural network exhibited pronounced disruption upon exposure to ammonium hydroxide, supported by physicochemical changes, the weakening of OH and SO3H absorption bands in FT-IR spectra, and optical microscopy-confirmed morphological alterations. Drug-release studies revealed highly accelerated celecoxib release (up to 86%) from NH4OH-treated gels compared to only 33% under normal physiological conditions, demonstrating strong ammonia-triggered responsiveness and high site-selective delivery. In vivo anti-inflammatory evaluation further confirmed enhanced therapeutic potency arising from the synergistic interaction between celecoxib and KC, while cell-line assays validated the formulation’s favorable safety profile. Although long-term stability and pharmacokinetic assessments are required for clinical translation, this study establishes KC as a dual-functional, smart, and ammonia-responsive system, offering a novel mechanistic framework for targeted, sustained, and effective treatment of ammonia-associated inflammatory disorders.