{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T23:26:41Z","timestamp":1781220401669,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cutaneous leishmaniasis (CL) is treated with painful intralesional injections of meglumine antimoniate (MA). With the aim of developing an alternative topical treatment for CL, a gel-based formulation with 30% MA was prepared and its physicochemical properties, stability and rheological behavior were studied. The following were assessed: drug release on propylene hydrophilic membranes ex vivo human skin permeation, tolerance in healthy volunteers, cytotoxicity in three cell lines and anti-leishmanial activity against Leishmania infantum promastigotes and amastigotes. The MA gel formulation was found to have suitable pH, and good spreadability and stability. Low quantities of pentavalent antimony (SbV) were observed in release and permeation tests, whereas retention was high in both non-damaged and damaged skin (71,043.69 \u00b1 10,641.57 and 10,728 \u00b1 2254.61 \u00b5g\/g\/cm2 of SbV, respectively). The formulation did not have a toxic effect on the cell lines, and presented lower SbV IC50 values against amastigotes (15.76 \u00b1 4.81 \u00b5g\/mL) in comparison with the MA solution. The high amount of drug retained in the skin and the SbV IC50 values obtained suggest that this semi-solid dosage form has potential as an alternative treatment of CL.<\/jats:p>","DOI":"10.3390\/pharmaceutics11110613","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T11:24:32Z","timestamp":1573817072000},"page":"613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis"],"prefix":"10.3390","volume":"11","author":[{"given":"Diana","family":"Berenguer","sequence":"first","affiliation":[{"name":"Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-5992","authenticated-orcid":false,"given":"Magdalena","family":"Alcover","sequence":"additional","affiliation":[{"name":"Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Sessa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyda","family":"Halbaut","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carme","family":"Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Fisa","sequence":"additional","affiliation":[{"name":"Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana Cristina","family":"Calpena-Campmany","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3522-5598","authenticated-orcid":false,"given":"Cristina","family":"Riera","sequence":"additional","affiliation":[{"name":"Department of Biology, Health and Environment, Laboratory of Parasitology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40249-018-0444-1","article-title":"Innovation in neglected tropical disease drug discovery and development","volume":"7","author":"Weng","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Janin, J., den Boer, M., and WHO Leishmaniasis Control Team (2012). Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.4269\/ajtmh.17-0769","article-title":"Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean Area","volume":"98","author":"Alcover","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4103\/tp.TP_1_19","article-title":"Cutaneous leishmaniasis in Bikaner, India: Clinicoepidemiological profile; parasite identification using conventional, molecular methods and CL DetectTM rapid test, a new Food and Drug Administration-approved test","volume":"9","author":"Rajni","year":"2019","journal-title":"Trop. Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Olliaro, P., Vaillant, M., Arana, B., Grogl, M., Modabber, F., Magill, A., Lapujade, O., Buffet, P., and Alvar, J. (2013). Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002130"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1128\/AAC.01319-08","article-title":"Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB\/c Mice","volume":"53","author":"Jaafari","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"(2019, October 09). Royal Society of Chemistry. Available online: https:\/\/doi.org\/10.1039\/9781788010177-00001.","DOI":"10.1039\/9781788010177-00001"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1017\/S0031182017000130","article-title":"Topical tamoxifen in the therapy of cutaneous leishmaniasis","volume":"145","author":"Trinconi","year":"2018","journal-title":"Parasitology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alexandrino-Junior, F., Silva, K.G.H.E., Freire, M.C.L.C., Lione, V.O.F., Cardoso, E.A., Marcelina, H.R., Genre, J., Oliveira, A.G., and Egito, E.S.T.D. (2019). A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050200"},{"key":"ref_10","first-page":"538","article-title":"Topical treatment for cutaneous leishmaniasis","volume":"3","author":"Garnier","year":"2002","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_11","first-page":"200","article-title":"Topical Treatment of Cutaneous Leishmaniasis in Israel, Part 1","volume":"23","author":"Zur","year":"2019","journal-title":"Int. J. Pharm. Compd."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/1523-1747.ep12696697","article-title":"Topical treatment of cutaneous leishmaniasis","volume":"87","author":"Livshin","year":"1986","journal-title":"J. Investig. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1056\/NEJMoa1202657","article-title":"Topical paromomycin with or without gentamicin for cutaneous leishmaniasis","volume":"368","author":"Guedri","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sosa, N., Pascale, J.M., Jim\u00e9nez, A.I., Norwood, J.A., Kreishman-Detrick, M., Weina, P.J., Lawrence, K., McCarthy, W.F., Adams, R.C., and Scott, C. (2019). Topical paromomycin for New World cutaneous leishmaniasis. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007253"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1086\/516267","article-title":"Topical paromomycin\/methylbenzethonium chloride plus parenteral meglumine antimoniate as treatment for American cutaneous leishmaniasis: Controlled study","volume":"26","author":"Soto","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/08982100903015025","article-title":"Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis","volume":"20","author":"Carneiro","year":"2010","journal-title":"J. Liposome Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2217\/nnm.14.102","article-title":"Developing cutaneous applications of paromomycin entrapped in stimuli-sensitive block copolymer nanogel dispersions","volume":"10","author":"Naveros","year":"2015","journal-title":"Nanomedicine (Lond.)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1128\/AAC.42.12.3092","article-title":"Efficacious topical treatment for murine cutaneous leishmaniasis with ethanolic formulations of amphoteicin B","volume":"42","author":"Frankenburg","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, L., V\u00e9lez, I., Asela, C., Cruz, C., Alves, F., Robledo, S., and Arana, B. (2018). A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006653"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0035-9203(99)90192-X","article-title":"Topical treatment with hexadecylphosphocholine (Miltex) efficiently reduces parasite burden in experimental cutaneous leishmaniasis","volume":"93","author":"Klenner","year":"1999","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1080\/10717544.2018.1494222","article-title":"Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of leishmaniasis: Macrophage as a target cell","volume":"25","author":"Dar","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.exppara.2014.04.013","article-title":"Use of topical liposomes containing meglumine antimoniate (Glucantime) for the treatment of L. major lesion in BALB\/c mice","volume":"143","author":"Khamesipour","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.exppara.2019.03.004","article-title":"The activity of encapsulated meglumine antimoniate in stearylamine-bearing liposomes against cutaneous leishmaniasis in BALB\/c mice","volume":"200","author":"Moosavian","year":"2019","journal-title":"Exp. Parasitol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0014-827X(01)01055-2","article-title":"Stability studies of new cosmetic formulations with vegetable extracts as functional agents","volume":"56","author":"Anchisi","year":"2001","journal-title":"Farmaco"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.jpba.2005.12.024","article-title":"Development and stability of semisolid preparations based on a supercritical CO2 Arnica extract","volume":"41","author":"Bilia","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ejps.2018.01.045","article-title":"Topical formulations of delta-aminolevulinic acid for the treatment of actinic keratosis: Characterization and efficacy evaluation","volume":"115","author":"Risaliti","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1208\/s12249-016-0529-8","article-title":"Development of Clotrimazole Multiple W\/O\/W Emulsions as Vehicles for Drug Delivery: Effects of Additives on Emulsion Stability","volume":"18","author":"Calpena","year":"2017","journal-title":"AAPS Pharm. Sci. Tech."},{"key":"ref_28","unstructured":"(2008). Council regulation (EC) no 440\/2008 Test guideline for skin absorption: In vitro method (B45). J. Eur. Union, 142, 438\u2013443."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"(2013). World medical association declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/srt.12016","article-title":"International guidelines for the in vivo assessment of skin properties in non-clinical settings: Part 2. Transepidermal water loss and skin hydration","volume":"19","author":"Stefaniak","year":"2013","journal-title":"Skin. Res. Technol."},{"key":"ref_31","first-page":"1","article-title":"Application of Quantum Dots to the Study of Liposome Targeting in Leishmaniasis and Malaria","volume":"2","author":"Pujol","year":"2014","journal-title":"Int. J. Theoret. Appiel. Nanotech."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1006\/expr.2000.4537","article-title":"Leishmania infantum: Stage-specific activity of pentavalent antimony related with the assay conditions","volume":"95","author":"Riera","year":"2000","journal-title":"Exp. Parasitol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0001-706X(01)00125-5","article-title":"In vitro activity of pentavalent antimony derivates on promastigotes and intracellular amastigotes of Leishmania infantum strains from humans and dogs in Spain","volume":"79","author":"Riera","year":"2001","journal-title":"Acta Trop."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jaad.2014.09.014","article-title":"Cutaneous and mucocutaneous leishmaniasis: Differential diagnosis, diagnosis, histopathology, and management","volume":"73","author":"Handler","year":"2015","journal-title":"J. Am. Acad Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ejps.2015.07.003","article-title":"The effect of rheological behavior and microstructure of the emulgels on the release and permeation profiles of Terpinen-4-ol","volume":"78","author":"Dong","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sosa, L., Calpena, A.C., Silva-Abreu, M., Espinoza, L.C., Rinc\u00f3n, M., Bozal, N., Domenech, O., Rodr\u00edguez-Lagunas, M.J., and Clares, B. (2019). Thermoreversible Gel-Loaded Amphotericin B for the treatment of Dermal and Vaginal Candidiasis. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11070312"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53671","DOI":"10.1039\/C5RA08374E","article-title":"Vitamin E TPGS based nanogel for the skin targeting of high molecular weight anti-fungal drug: Development and in vitro and in vivo assessment","volume":"5","author":"Kaur","year":"2015","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/jid.1983.12","article-title":"Epidermal lipids, barrier function, and desquamation","volume":"80","author":"Elias","year":"1983","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/jid.1965.59","article-title":"Chemical structure and skin penetrating capacity of a short series of organic phosphates and phosphoric acid","volume":"44","author":"Marzulli","year":"1965","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/1523-1747.ep12277592","article-title":"Solute structure-permeability relationships in human stratum corneum","volume":"93","author":"Anderson","year":"1989","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","first-page":"456","article-title":"Skin density in the hairless rat. Evidence of regional differences","volume":"3","author":"Rins","year":"1991","journal-title":"Eur. J. Drug Metab. Pharmacokinet."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/11\/613\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:34:42Z","timestamp":1760189682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/11\/613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,15]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["pharmaceutics11110613"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11110613","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,15]]}}}