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

Area of Science:

• Biochemistry
• Materials Science
• Pharmaceutical Chemistry

Background:

• Rising antifungal resistance poses a significant global health threat.
• Existing antifungals like Amphotericin B have limitations including poor solubility and toxicity.
• Alginates, particularly oligoguluronates, show promise as drug delivery agents due to their properties.

Purpose of the Study:

• To develop novel bifunctional antifungal compounds by conjugating Amphotericin B with alginates.
• To improve the solubility and reduce the toxicity of Amphotericin B.
• To assess the antifungal activity and safety of the developed conjugates.

Main Methods:

• Synthesis of two types of Alginate-Amphotericin B conjugates using low molecular weight oligoguluronates.
• Conjugation strategies involved linking through the reducing end of alginate to either the carboxylic acid or amine group of Amphotericin B.
• Evaluation of conjugate toxicity on liver (HepG2) and kidney (LLC-PK1) cells.

Main Results:

• Successfully synthesized Alginate-Amphotericin B conjugates with improved water solubility.
• Demonstrated reduced toxicity of the conjugates towards liver and kidney cells compared to free Amphotericin B.
• The conjugates maintained significant antifungal activity.

Conclusions:

• Alginate-Amphotericin B conjugates represent a promising strategy for developing safer and more effective antifungal agents.
• The improved physicochemical properties and maintained efficacy suggest potential for clinical applications in combating fungal infections.
• This approach addresses the critical need for new treatments against drug-resistant fungi.