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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schwartz, Juana Moreno, Esther Fernández, Celia Navarro-Blasco, Iñigo Nguewa, Paul A. Palop, Juan A. Irache, Juan M. Sanmartín, Carmen Espuelas, Socorro |
| Description | Country affiliation: Spain Author Affiliation: Schwartz J ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain); Moreno E ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain.); Fernández C ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain.); Navarro-Blasco I ( Chemistry and Soil Sciences Department, University of Navarra, 31008 Pamplona, Spain.); Nguewa PA ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain.); Palop JA ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain); Irache JM ( Pharmacy and Pharmaceutical Technology Department, University of Navarra, 31008 Pamplona, Spain.); Sanmartín C ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain); Espuelas S ( Institute of Tropical Health, University of Navarra, 31008 Pamplona, Spain) |
| Abstract | Topical therapy is the ideal outpatient treatment of cutaneous leishmaniasis (CL) because of the ease of administration and lower cost. It could be suitable as monotherapy for localized cutaneous leishmaniasis (LCL) or in combination with systemic therapies for more severe forms of the disease. Although paromomycin (PM) ointment can be recommended for the treatment of LCL caused by Leishmaniamajor, a more effective topical treatment should be achieved regarding the physicochemical properties of this aminoglucoside and its rather poor intrinsic antileishmanial activity, that hampers the accumulation of enough amount of drug in the dermis (where the infected macrophages home) to exert its activity. In this work, we determined a 50% effective dose of 5.6 µM for a novel compound, bis-4-aminophenyldiselenide, against L. major intracellular amastigotes. This compound and PM were formulated in chitosan hydrogels and ex vivo permeation and retention studies in the different skin layers were performed with pig ear skin in Franz diffusion cells. The results showed that less than 2-4% of the diselenide drug penetrated and permeated through the skin. In contrast, the percentage of PM penetration was about 25-60% without important retention in the skin. When topically applied to lesions of L. major infected BALB/c mice, the novel diselenide chitosan formulation was unable to slow lesion progression and reduce parasite burden. Considerations during the process of novel drug development and formulation discovery algorithm for CL are discussed. |
| File Format | HTM / HTML |
| ISSN | 09280987 |
| Volume Number | 62 |
| e-ISSN | 18790720 |
| Journal | European Journal of Pharmaceutical Sciences |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-10-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Chemistry Discipline Pharmacology Aniline Compounds Administration & Dosage Antiprotozoal Agents Drug Carriers Hydrogels Leishmaniasis, Cutaneous Drug Therapy Organoselenium Compounds Administration, Topical Chemistry Animals Chitosan Female Leishmania Major Parasitology Macrophages, Peritoneal Drug Effects Mice, Inbred Balb C Parasite Load Skin Metabolism Skin Absorption Swine Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science |
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