The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.

Current cancer chemotherapy is associated with many side effects and, in some cases, drug resistance, which makes the search for new active molecules and drug delivery strategies imperative. Carbamazepine is an antiepileptic compound that has shown efficacy against breast cancer cell lines. In this study, it was incorporated into layered double hydroxide nanoclays, the percentage of drug loading was increased compared to previous research, and the clays were impregnated with magnetic Fe₃O₄ nanoparticles. The goal of the magnetic Fe₃O₄-impregnation was to direct the nanocomposites to the therapeutic target with an external magnetic field. The nanoclay-carbamazepine composites had a carbamazepine loading of 51 %, and the nanoclay-carbamazepine-nanoparticles had a drug loading of 13 % due to the addition of more ingredients. The structure of the composites was analyzed by X-ray diffraction and Scherrer equation, showing a layered double hydroxide organization with crystal sizes of 9–15 nm; from transmission electron microscopy, the final compounds showed a particle size of 97–158 nm, small enough for systemic circulation. In vibrating sample magnetization studies, the composites showed a superparamagnetic behavior with high magnetic saturation (9–17 emu/gr), which should allow a good material attraction by an external magnetic field located near the tumor. In vitro drug release studies were done in Franz cells and measured by UV/Vis spectrophotometry; they showed that carbamazepine release from the nanocomposites responds to the media pH: a good drug release at the lysosome pH and slow release at the blood pH. Finally, the efficacy was tested in vitro in MDA-MB-231 breast cancer cells, and the composites showed an enhanced efficacy in comparison with that produced by the free drug (96 % and 62 % of cell inhibition respectively). Carbamazepine administered with magnetic clays as a carrier is a promising treatment for breast cancer, and further studies should be done to measure the arrival time and the efficacy in vivo.

An efficacious topical treatment for cutaneous leishmaniasis (CL) is highly desirable but still an ongoing challenge. Systemic risedronate (Ris) has been reported to have anti-leishmanial properties and Eudragit EPO (EuE) has shown in vitro activity against L. (L.) amazonensis. The aim of this work was to investigate the in vivo efficacy of topical Ris and EuE-Ris complexes on CL. Surface charge and Ris release kinetics from the different dispersions were analyzed. BALB/c mice were infected intradermally with promastigotes of L. (L.) amazonensis. Ulcers were treated with Ris or EuE-Ris hydrogels. All the lesions that received topical Ris or EuE-Ris showed an improvement with respect to control: reduction of ulcer average size, cicatrization, flattened edges and no signs of necrosis. In addition, a marked parasitic inhibition of 69.5 and 73.7% was observed in the groups treated with Ris and EuE-Ris, respectively, with the IgG2a levels indicating a tendency towards cure. The results are promising and the system should now be enhanced to achieve total parasite elimination.

A male rural worker with cutaneous leishmaniasis (CL) was initially treated with repeated cy-cles of Meglumine Antimoniate (Glucantime®) and two cycles of Amphotericin B deoxycholate during a three-year period. However, the patient remained with two active lesions. An experi-mental topical treatment with liposomal Miltefosine was tested. The efficacy was determined from the MD’s inspection of the patient and analysis of the lesions’ photographic images, le-sions samples culture, and anti-Leishmania antibodies quantification. The parasites from the patient were isolated. The parasites were typified as Leishmania (Viannia) braziliensis, and their susceptibility to Miltefosine, Meglumine Antimoniate, and Amphotericin B was measured. The wound healing was initially good with the topical treat-meant, but the clinical cure was achieved only with a combination of the topical liposomal Miltefosine and intravenous Amphotericin B. Of note, the treatment efficacy was strongly corre-lated with the degree of stress suffered by the patient. To our knowledge, this is the first report on using a topical Miltefosine formulation on a CL patient.