Work

Alginate-Amphotericin B bifunctional conjugates have improved solubility and reduced toxicity

Year: 2026

Type: article

Abstract: Alginates are a family of linear anionic polysaccharides produced by brown algae and some bacteria which consist of 1→4 linked β-d-mannuronic acid (M), and its C5-epimer α-l-guluronic acid (G). Research has shown that oligoguluronates possess biofilm disruption properties, which combined with their high water solubility and low toxicity, represent ideal candidates for creating novel bifunctional antifungal compounds. The progressive increase in antifungal resistance is a major global human health threat. Moreover, fungal biofilm infections are up to 1000-fold more tolerant to antifungal agents than fungal cells in planktonic growth. This intrinsic resistance illustrates the need to develop improved antifungal drugs with greater efficacy against biofilm growth, while also reducing the potential for drug toxicity, resistance and tolerance. Amphotericin B is a polyene macrolide antifungal with broad specificity but has poor water solubility and is limited by infusion-related reactions and nephrotoxicity. In this work, we developed two types of Alginate-Amphotericin B conjugates with low molecular weight oligoguluronates conjugated through the reducing end. Conjugation to amphotericin B was through the carboxylic acid group or the amine group. The Alginate-Amphotericin B conjugates have reduced toxicity towards human liver cells (HepG2) and kidney cells (LLC-PK1) and highly improved solubility characteristics, while maintaining anti-fungal activity.

Source: Carbohydrate Polymers

DOI: 10.1016/j.carbpol.2026.125105