Amphotericin B and Curcumin Co-Loaded Porous Microparticles as a Sustained Release System against Candida albicans

Abstract

Amphotericin B (AMB) is an antifungal drug used for serious fungal infections. However, AMB has adverse reactions such as nephrotoxicity, which limit the clinical application of AMB alone or in combination with other antifungal drugs. Nano or micro drug delivery systems (DDS) have been proven to be effective in reducing the toxic and side effects of drugs. Further, the combination of AMB with other compounds with antifungal activity, such as curcumin (CM), may enhance the synergistic effects. Herein, AMB and CM were co-loaded into porous poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) to prepare AMB/CM-PLGA MPs. The AMB/CM-PLGA MPs showed a remarkably reduced hemolysis (62.2 ± 0.6%) compared to AMB (80.9 ± 1.1%). The nephrotoxicity of AMB/CM-PLGA MPs is significantly lower than that of AMB. In vitro, AMB/CM-PLGA MPs had better inhibitory effects on the adhesion and biofilm formation of Candida albicans compared with AMB. Experiments on mice infected with C. albicans showed that AMB/CM-PLGA MPs have a better therapeutic effect than AMB in vivo. In summary, AMB/CM-PLGA MPs may be a novel and promising therapeutic candidate for fungal infection.

Lipase-Responsive Amphotericin B Loaded PCL Nanoparticles for Antifungal Therapies

“…The MIC and disk diffusion assays were utilized to investigate the antifungal ability of AMB and PCL-AMB NPs against C. albicans ATCC 10231. The MIC is defined as the lowest concentration inhibiting the microorganism’s growth [ 7 ]. The results show that AMB exhibited an MIC of 0.25 µg/mL ( Figure S2B ), which is consistent with published studies [ 42 , 43 ].…”

“…Due to these similarities, most antifungal drugs are also cytotoxic thus, non-selective antifungal therapy could lead to mammalian cell toxicity. For example, AMB interacts with cholesterol in mammalian cell membranes, and as a result, the drug can cause nephrotoxicity and cardiotoxicity [ 7 , 8 ]. The antifungal mechanism of action of AMB involves the interaction of the drug with the ergosterol in the fungal cell membrane, thereby altering their cell structures and permeability [ 7 , 9 ].…”

“…For example, AMB interacts with cholesterol in mammalian cell membranes, and as a result, the drug can cause nephrotoxicity and cardiotoxicity [ 7 , 8 ]. The antifungal mechanism of action of AMB involves the interaction of the drug with the ergosterol in the fungal cell membrane, thereby altering their cell structures and permeability [ 7 , 9 ]. Due to its poor water solubility and bioavailability, AMB is required to be administered in a high dose [ 10 ].…”

“…On-demand delivery and release platforms for antifungal agents are considered a way forward to treat fungal infections effectively. This can be achieved by using appropriate techniques to encapsulate antifungals in stimuli-responsive materials [ 7 ]. Herein, we report the synthesis of PCL nanoparticles for the lipase-triggered release of AMB and demonstrate their responsiveness to fungal lipases, efficacy in killing clinically relevant fungal species, and cytocompatibility with primary human dermal fibroblasts.…”

The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans

“…These findings corroborate data in the available literature. The MIC of CUR by the broth microdilution method was also equal to 256 µg/mL against C. albicans ATCC 10231 in the study conducted by Xue et al [ 44 ]. In another study, MCZ’s MIC50 and MIC80, defined as the lowest concentrations to inhibit growth by 50% to 80%, were equal to 2 µg/mL and 4 µg/mL, in this order, against the same reference strain of C. albicans [ 45 ].…”