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Objectives: Topical treatment for cutaneous leishmaniasis (CL) would be useful for treatment of some forms of the disease. The aim of this study was to develop and then evaluate a topical miltefosine gel for anti-leishmanial activity and toxicity in BALB/c mice infected with New World (NW)-CL species., Methods: A Carbopol-based gel of 0.5% miltefosine was prepared and physicochemical (colour, pH, consistency and antioxidant activity) and stability properties were determined using standard methodologies. Anti-leishmanial activities for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis were determined both in cultured parasites and in infected BALB/c mice after topical miltefosine gel treatment administered for 20 days. The gel was evaluated for its capacity to inhibit parasites at a 50% level after 3 days of treatment in vitro, and its capacity to reduce lesion size (mm2) and parasitic load after 20 days of treatment. Dermal irritation, contact hypersensitivity (CHS), clinical biochemical profile and the weight of the animals were determined after treatment., Results: The 0.5% miltefosine gel was transparent, homogeneous, colourless, of neutral pH, spreadable and stable at 4°C for at least 3 months. It was active against parasites in vitro and in vivo, reducing CL lesion size by 84%-100% with no detected parasites. No signs of irritation, CHS or changes in weight, food intake, urea or transaminase serum levels were observed after treatment., Conclusions: The topical 0.5% miltefosine gel formulation was efficacious and non-toxic when administered topically in NW-CL murine models. This miltefosine formulation could be an appropriate candidate for further development., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ultradeformable liposomes (UDLs) containing sodium cholate as edge activator could be an appropriate skin drug-delivery system for chloroaluminum phthalocyanine (ClAlPc) during photodynamic therapy (PDT) against cutaneous leishmaniasis (CL). The aim of this work was to study cell internalization, reactive oxygen species (ROS) production, and toxicity/genotoxicity and transdermal delivery of UDL-ClAlPc, and to determine whether PDT was able to induce anti-leishmanial activity in Leishmania (Viannia) braziliensis experimental models. Prepared liposomes had an average size of 118.39 nm, zeta potential of -37.83 mV, and polydispersity index of 0.15. Liposomal internalization (red fluorescence inside cells), ROS generation (green fluorescence by 2,7-dichlorodihydrofluorescein diacetate [DCFH-DA] cleavage) and non-specific DNA damage (photo-comets) were observed after PDT. Transdermal delivery of ClAlPc, measured by in vitro diffusion experiments through BALB/c skin, showed that UDL-ClAlPc was able to deliver very low quantities of ClAlPc (<1%) to deep skin layers. PDT using UDL-ClAlPc induced photodamage in mammalian cells (J774, THP-1, and NIH-3T3), promastigotes, and intracellular amastigotes without a selective response against amastigotes (selective index ≥1). Topical once-daily ClAlPc-UDL plus visible-light irradiation (20 J/cm 2 ) twice weekly for 3 weeks was ineffective against L. (V.) braziliensis-infected BALB/c mice, whereas miltefosine 30 mg/kg/day orally for 10 days healed the lesions and scars, without parasites observed on the slides. Even though UDLs preserved ClAlPc photoactivities and were able to deliver ClAlPc to dermis, they were unable to result in healing of CL-infected mice after PDT. Experiments using different CL animal models and liposomes with increased skin permeability abilities are recommended., (Copyright © 2018. Published by Elsevier Inc.)