In vitro Inhibition of Fungal Activity by Macrophage-Mediated Sequestration and Release of Encapsulated Amphotericin B Nanosupension in Red Blood Cells

The efficacy of antifungal treatment has been diminished by the biodistribution limitations of amphotericin B (AmB) due to its pharmacological profile, as well as the severe side effects it causes. A cellular drug‐delivery system, which incorporates human erythrocytes (RBCs) loaded with an AmB nanosuspension (AmB‐NS), is developed in order to improve antifungal treatment. AmB‐NS encapsulation in RBCs is achieved by using hypotonic hemolysis, leading to intracellular AmB amounts of 3.81 ± 0.47 pg RBC−1 and an entrapment efficacy of 15–18%. Upon phagocytosis of AmB‐NS–RBCs, leukocytes show a slow AmB release over ten days, and no alteration in cell viability. This results in an immediate, permanent inhibition of intra‐ and extracellular fungal activity. AmB‐NS–RBC‐leukocyte‐mediated delivery of AmB is efficient in amounts 1000 times lower than the toxic dose. This drug‐delivery method is effective for the transport of water‐insoluble substances, such as AmB, and this warrants consideration for further testing. A cellular drug‐delivery system is developed that incorporates human erythrocytes loaded with an amphotericin B nanosuspension in order to improve antifungal treatment. The loaded erythocytes are recognized by phagocytes through exposed phosphatidylserine on their surfaces (see image). This system offers opportunities to reintegrate potent agents with an unfavorable cytotoxicity profile into clinical practice.