Cholesterol improves stability of amphotericin B nanoemulsion: promising use in the treatment of cutaneous leishmaniasis.

Aim: Amphotericin B (AmB) is an antileishmanial drug with high toxicity; however, this drawback might overcome by decreasing the AmB self-aggregation state. This work aimed at evaluating the influence of cholesterol on the aggregation state of AmB loaded in a nanoemulsion (NE-AmB) for the treatment of cutaneous leishmaniasis. NE-AmB (1, 4 and 8 mg/kg/day) was administered intravenously to animals infected by Leishmania major every 2 days for a total of five injections. Results: Ultraviolet-visible spectroscopy and circular dichroism studies demonstrated that cholesterol reduced AmB aggregation state in NE. NE-AmB was stable after 180 days, and its hemolytic toxicity was lower than that observed for the conventional AmB. NE-AmB administered intravenously into animals infected by Leishmania major at 8 mg/kg was capable of stabilizing the lesion size and reducing the parasitic load. Conclusion: These findings support the NE potential as a stable nanocarrier for AmB in the treatment of cutaneous leishmaniasis.

Nanostructured lipid carriers enhances the safety profile of tretinoin: in vitro and healthy human volunteers' studies.

Aim: To enhance the tretinoin (TRE) safety profile through the encapsulation in nanostructured lipid carriers (NLC). Materials & methods: NLC-TRE was developed using a 23 experimental factorial design, characterized (HPLC, dynamic light scattering, differential scanning calorimetry, x-ray diffraction analysis, transmission electron microscopy, cryo-transmission electron microscopy) and evaluated by in vitro studies and in healthy volunteers. Results: The NLC-TRE presented spherical structures, average particle size of 130 nm, zeta potential of 24 mV and encapsulation efficiency of 98%. The NLC-TRE protected TRE against oxidation (p < 0.0001) and promoted epidermal targeting (p < 0.0001) compared with the marketed product, both 0.05% TRE. The in vitro assay on reconstructed human epidermis and the measurement of transepidermal water loss in healthy volunteers demonstrated an enhanced safety profile in comparison to the marketed product (p < 0.0002). Conclusion: The NLC-TRE enhances the epidermal targeting and safety profile of TRE, representing a potential safer alternative for the topical treatment of skin disorders using TRE.

Polarity-sensitive nanocarrier for oral delivery of Sb(V) and treatment of cutaneous leishmaniasis.

There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb-N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime(®) given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis.

Novel vesicular and particulate drug delivery systems for topical treatment of acne.

BACKGROUND: The efficacy of the antiacne topical drugs is well established. The local side effects, however, mainly cutaneous irritation, erythema, dryness, peeling and scaling, remain major problems. Novel vesicular and particulate drug delivery systems have been proposed to reduce the side effects of drugs commonly used in the topical treatment of acne. OBJECTIVE: This review focuses on the development and evaluation of antiacne drug-loaded vesicular and particulate delivery systems (liposomes, polymeric microspheres and solid lipid nanoparticles) for topical treatment, their advantages and challenges. METHODS: All the literature available was reviewed to highlight the potential of these novel systems for the topical treatment of acne. CONCLUSION: The encapsulation of antiacne drugs in vesicular and particulate delivery systems represents an innovative alternative to minimize side effects, while preserving their efficacy. This can be obtained by the capacity of these systems to provide controlled release or to improve the drug penetration into skin or even into the pilosebaceous unit.