Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice.

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N=6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA-DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases.

Successful strategy for targeting the central nervous system using magnetic albumin nanospheres.

This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.