Nanoemulsions containing amphotericin b and paromomycin for the treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a vector-borne disease characterized by skin lesions that can evolve into high-magnitude ulcerated lesions. Thus, this study aimed to develop an innovative nanoemulsion (NE) with clove oil, Poloxamer® 407, and multiple drugs, such as amphotericin B (AmB) and paromomycin (PM), for use in the topical treatment of CL. METHODS: Droplet size, morphology, drug content, stability, in vitro release profile, in vitro cytotoxicity on RAW 264.7 macrophages, and antileishmanial activity using axenic amastigotes of Leishmania amazonensis were assessed for NEs. RESULTS: After optimizing the formulation parameters, such as the concentration of clove oil and drugs, using an experimental design, it was possible to obtain a NE with an average droplet size of 40 nm and a polydispersion index of 0.3, and these parameters were maintained throughout the 365 days. Furthermore, the NE showed stability of AmB and PM content for 180 days under refrigeration (4 °C), presented a pH compatible with the skin, and released modified AmB and PM. NE showed the same toxicity as free AmB and higher toxicity than free PM against RAW 264.7 macrophages. The same activity as free AmB, and higher activity than free PM against amastigotes L. amazonensis. CONCLUSION: It is possible to develop a NE for the treatment of CL; however, complementary studies regarding the antileishmanial activity of NE should be carried out.

Bloodwood: the composition and secreting-site of the characteristic red exudate that gives the name to the Swartzia species (Fabaceae).

The Swartzia species are commonly known as bloodwood due to the red exudate released from the stem after injury. This exudate has aroused great interest, and an integrative study is essential to describe it in detail. Thus, this work aimed to identify the red exudate's secreting-site in S. flaemingii and S. langsdorffii, and determine if it is a latex or a resin. Samples of the stem bark and the secondary xylem were prepared for histological analysis. Fresh exudates were dissolved in deuterated methanol and analyzed by 1H-NMR; other samples were resuspended in MeOH:H2O (9:1), partitioned with organic solvents and analyzed by direct infusion mass spectrometry. Total phenolic and total flavonoid contents were determined spectrophotometrically, and antioxidant capacity was determined using ferric reducing antioxidant power assay. The results showed that the exudate is a red latex produced by articulated laticifers located among the phloem cells. The latex is composed of sucrose, catechin glucosides, chlorophyll derivatives, and hederagenin-type saponins. Both samples of S. flaemingii and S. langsdorffii presented high amounts of phenolics and flavonoids, as well as a strong antioxidant capacity. The anatomical study showed that the secreting-site of the Swartzia red exudates were laticifers. This finding allows us to exclude other substances such as resin or oleoresin, generally produced by secretory cavities or ducts. Furthermore, since laticifers are rare in Fabaceae, this finding is significant, and represents an essential taxonomic feature. The showy red color is due to the large amounts of flavonoids. This latex probably has a protective role against microorganisms and photodamage. The bioactive potential of this exudate inspires further studies, which may boost the economic importance of Swartzia.

Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy for Leishmania spp.

Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic® F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.