Anidulafungin liposome nanoparticles exhibit antifungal activity against planktonic and biofilm Candida albicans

Abstract

Fungal infections can cause significant patient morbidity and mortality. Nanoparticle therapeutics have the potential to improve treatment of these infections. Here we report the development of liposomal nanoparticles incorporating anidulafungin, a potent antifungal, with the goal of increasing its solubility and aiding in localization to fungi. Liposomes were fabricated with three concentrations of anidulafungin yielding monodisperse ~100 nm unilamellar vesicles. All three formulations inhibited planktonic Candida albicans growth at a minimum inhibitory concentration equivalent to free drug. All three formulations also disrupted preformed C. albicans biofilms, reducing fungal burden by as much as 99%, exhibiting superior biofilm disruption compared with free drug. Liposome formulations tested in vivo in C. albicans infected Galleria mellonella wax moth larvae demonstrated increased survival compared to free drug equivalents, leading to a survival of 33 to 67% of larvae over 7 days depending on the liposome utilized compared with only 25% survival of larvae administered free drug. Liposomal formulations along with free anidulafungin did not cause red blood cell lysis. Ultimately, the liposome formulations reported here increased anidulafungin solubility, displayed promising efficacy against planktonic and biofilm C. albicans, and improved the survival of C. albicans–infected G. mellonella compared to free anidulafungin.

DectiSomes: Glycan Targeting of Liposomal Drugs Improves the Treatment of Disseminated Candidiasis

“…In published studies using neutropenic mouse models of candidiasis a dose of 4 to 25 mg/kg AFG produces at least a 10-fold drop in fungal burden of in the kidneys within 24 to 48 hr (32,38). A recent study prepared AFG-LLs loaded with 5.2 moles percent AFG relative to moles of liposomal lipid (39). In their wax moth model of candidiasis, the prophylactic administration of AFG-LLs delivering 2.6 mg/kg AFG significantly improved insect survival relative to an equivalent prophylactic dose of free AFG (39).…”

“…A recent study prepared AFG-LLs loaded with 5.2 moles percent AFG relative to moles of liposomal lipid (39). In their wax moth model of candidiasis, the prophylactic administration of AFG-LLs delivering 2.6 mg/kg AFG significantly improved insect survival relative to an equivalent prophylactic dose of free AFG (39). We prepared AFG-LLs with 6.2 moles percent AFG (Supplemental Table ST1) and coated some with Dectin-2 to make DEC2-AFG-LLs.…”

Advances in Biomaterials for the Prevention and Disruption of Candida Biofilms

“…Liposomal amphotericin B has also been immobilized on biomaterial surfaces for the prevention of biofilm formation (Alves et al, 2019). In our recent work, we have shown that liposomes encapsulating anidulafungin, the latest echinocandin approved by the FDA, are effective against mature C. albicans biofilms, reducing metabolic activity to approximately 46% compared to untreated controls over 24 h. Biofilms treated with an equivalent concentration of free anidulafungin did not reduce metabolic activity, further emphasizing the importance of nanoformulations in the treatment of Candida biofilms (Vera-González et al, 2020).…”

Potent antifungal agents and use of nanocarriers to improve delivery to the infected site: A systematic review

“…Liposomal formulations of anidulafungin had higher solubility and thus better efficacy against planktonic and biofilm of C. albicans . Improved survival of Galleria mellonella infected with C. albicans has been reported on the use of the liposomal formulation as against free anidulafungin [47].…”