<p>Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of <em>Leishmania braziliensis</em> Infection</p>

Abstract

Background Leishmaniasis is a neglected disease, and the current therapeutic arsenal for its treatment is seriously limited by high cost and toxicity. Nanostructured lipid carriers (NLCs) represent a promising approach due to high drug loading capacity, controlled drug release profiles and superior stability. Here, we explore the efficacy of a unique pH-sensitive amphotericin B-loaded NLC (AmB-NLC) in Leishmania braziliensis infection in vitro and in vivo. Methods and Results AmB-NLC was assessed by dynamic light scattering and atomic force microscopy assays. The carrier showed a spherical shape with a nanometric size of 242.0 ± 18.3 nm. Zeta potential was suggestive of high carrier stability (−42.5 ± 1.5 mV), and the NLC showed ~99% drug encapsulation efficiency (EE%). In biological assays, AmB-NLC presented a similar IC 50 as free AmB and conventional AmB deoxycholate (AmB-D) (11.7 ± 1.73; 5.3 ± 0.55 and 13 ± 0.57 ng/mL, respectively), while also presenting higher selectivity index and lower toxicity to host cells, with no observed production of nitric oxide or TNF-α by in vitro assay. Confocal microscopy revealed the rapid uptake of AmB-NLC by infected macrophages after 1h, which, in association with more rapid disruption of AmB-NLC at acidic pH levels, may directly affect intracellular parasites. Leishmanicidal effects were evaluated in vivo in BALB/c mice infected in the ear dermis with L. braziliensis and treated with a pentavalent antimonial (Sb 5+ ), liposomal AmB (AmB-L) or AmB-NLC. After 6 weeks of infection, AmB-NLC treatment resulted in smaller ear lesion size in all treated mice, indicating the efficacy of the novel formulation. Conclusion Here, we preliminarily demonstrate the effectiveness of an innovative and cost-effective AmB-NLC formulation in promoting the killing of intracellular L. braziliensis . This novel carrier system could be a promising alternative for the future treatment of cutaneous leishmaniasis.

Optimization and Characterization of Low-Molecular-Weight Chitosan-Coated Baicalin mPEG-PLGA Nanoparticles for the Treatment of Cataract

“…In addition, the fluorescence intensity of the NPs is significantly enhanced after being coated with LCH. The rapid uptake of cells can help reduce the accumulation of drugs in healthy tissues, reduce toxicity, and prevent side-effects in order to improve the bioavailability of the eye …”

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

“…However, the application of AMB is limited because it is severely toxic to normal tissues and can cause various side effects, including infusion-related toxicity and chronic toxicity. In order to overcome the shortcomings of AMB, several drug delivery systems (DDS) have been developed, such as lipid formulations of AMB and AMB solubilized with sodium deoxycholate [ 8 , 9 ]. Furthermore, porous microparticles (MPs) were considered to be promising.…”