Design of amphotericin B oral formulation for antifungal therapy

Abstract

Amphotericin B (AmB) remains the ''gold standard'' for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

“…However, commercially available AmB lipid formulations for the treatment of invasive fungal infections are expensive and require parenteral administration, increasing length of hospital stay and healthcare costs. Therefore, the development of an orally available AmB formulation able to decrease the systemic toxicity of the drug, avoid infusion-related adverse events, improve patient compliance, and reduce the costs associated with commercial AmB formulations for intravenous administration is an urgent requirement [41,[158][159][160]. Lipid-based systems for AmB delivery which mainly developed over the last five years are summarized in Table 2 and will be further discussed in the next sections.…”

In Vitro Antileishmanial Activities of Olea europaea, Kigelia africana, Terminalia mollis, Croton Macrostachyus and Bridella micrantha, Kenyan Medicinal Plants

“…In the L. major infected BALB/c mice treated with Amphotericin B and T. mollis, large section of the liver showed normal physiology thus asserting the low toxicity of Amphotericin B and T. mollis to macrophage and cells. Low toxic effects of Amphotericin at the right doses has been previously reported mostly based on different mode of formulation [61][62][63]. However, the treatment with antimonials has several side effects, such as: pancreatitis, malaise, diarrhoea and cardiac arrhythmia [64] which means that even if they are of low toxicity to the cells, there is a need to search for safer alternatives.…”

New Approaches for Cryptococcosis Treatment

“…Despite AMB dose-limiting toxicity, it has remained the gold standard for treating disseminated life-threatening fungal infections [19]. Its fungicidal effect is associated with AMB binding to ergosterol in the membranes of fungal cell (Figure 1) [20,21]. AMB perturbs the membrane function, causing leakage of cellular contents, and leads to death by cellular dysfunction [20,21].…”

“…Its fungicidal effect is associated with AMB binding to ergosterol in the membranes of fungal cell (Figure 1) [20,21]. AMB perturbs the membrane function, causing leakage of cellular contents, and leads to death by cellular dysfunction [20,21]. The first commercially available formulation was Fungizone ® , a conventional micellar form of AMB and deoxycholate.…”