Polymer–Drug Conjugates for Treating Local and Systemic Fungal Infections

Abstract

In immunocompromised patients, fungal infections are the major cause of morbidity and mortality. Currently, three major classes of drugs—polyenes, azoles, and echinocandins—with different mechanisms of action are used as antifungals for systemic infections. However, these conventional drugs were reported to induce toxic effects due to their low specificity, narrow spectrum of activity and drug–drug interactions. Some of these limitations could be overcome by altering the properties of existing drugs through physical and chemical modifications. For example, modification of amphotericin B (AmB), a polyene antibiotic includes the micellar suspension of AmB in deoxycholic acid (Fungizone®), non-covalent AmB lipid complexes (ABLC™), liposomal AmB (AmBisome®), and AmB colloidal dispersion (Amphocil™). All these formulations ensure the smoother release of AmB accompanied by its restricted distribution in the kidney, thereby lowering its nephrotoxicity. Although various methods such as polymeric micelles, nanoparticles and dendrimers were explored for enhancing the efficacy of the antifungal drugs, polymer–drug conjugates of antifungal drugs have received more attention in recent years. Polymer–drug conjugates improve the aqueous solubility of water-insoluble drugs, are stable in storage and reduce the toxicity of highly toxic drugs and are capable of releasing the drug at the site of action. This chapter discusses the polymer conjugates of antifungal drugs, their merits, and demerits. Studies reported so far show that the polymer–drug conjugates have significant advantages compared to conventional dosage forms for antifungal therapy.