{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:22:17Z","timestamp":1780435337487,"version":"3.54.1"},"reference-count":58,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,2]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Leishmaniasis is a parasitic disease caused by <jats:italic>Leishmania<\/jats:italic> parasites. Meglumine antimoniate, or Glucantime, is the primary drug used to treat this disease. Glucantime with a standard painful injection administration route has high aqueous solubility, burst release, a significant tendency to cross into aqueous medium, rapid clearance from the body, and insufficient residence time at the injury site. Topical delivery of Glucantime can be a favorable option in the treatment of localized cutaneous leishmaniasis. In this study, a suitable transdermal formulation in the form of nanostructured lipid carrier (NLC)-based hydrogel containing Glucantime was prepared. In vitro drug release studies confirmed controllable drug release behavior for hydrogel formulation. An in\u00a0vivo permeation study on healthy BALB\/C female mice confirmed appropriate penetration of hydrogel into the skin and sufficient residence time in the skin. In vivo performance of the new topical formulation on the BALB\/C female mice showed a significant improvement in reduction of leishmaniasis wound size, lowering parasites number in lesions, liver, and spleen compared with commercial ampule. Hematological analysis showed a significant reduction of the drug\u2019s side effects, including variance of enzymes and blood factors. NLC-based hydrogel formulation is proposed as a new topical administration to replace the commercial ampule.<\/jats:p>","DOI":"10.4269\/ajtmh.23-0116","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T14:57:53Z","timestamp":1686581873000},"page":"301-314","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Topical Formulation of the Leishmaniasis Drug Glucantime as a Nanostructured Lipid Carrier-Based Hydrogel"],"prefix":"10.4269","volume":"109","author":[{"given":"Faranak","family":"Dehghani","sequence":"first","affiliation":[{"name":"Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafiseh","family":"Farhadian","sequence":"additional","affiliation":[{"name":"Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Mashayekhi Goyonlo","sequence":"additional","affiliation":[{"name":"Cutaneous Leishmaniasis Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Mycology, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"F1000Research","first-page":"750","article-title":"Leishmaniasis: a review","volume":"6","author":"Torres-Guerrero","year":"2017"},{"key":"b2","series-title":"Parasitol Res","first-page":"1","article-title":"Leishmaniasis treatment \u2013 a challenge that remains: a review","volume":"103","author":"Santos","year":"2008"},{"key":"b3","series-title":"BMC Infect Dis","first-page":"1","article-title":"Cutaneous leishmaniasis a neglected tropical disease: community knowledge, attitude and practices in an endemic area, northwest Ethiopia","volume":"19","author":"Tamiru","year":"2019"},{"key":"b4","series-title":"The Leishmaniases: Old Neglected Tropical Diseases, 1st edition","author":"Bruschi","year":"2018"},{"key":"b5","series-title":"J Nanobiotechnol","first-page":"1","article-title":"Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight","volume":"19","author":"Jamshaid","year":"2021"},{"key":"b6","series-title":"Southeast Asian J Trop Med Public Health","first-page":"502","article-title":"Glucantime efficacy in the treatment of zoonotic cutaneous leishmaniasis","volume":"42","author":"Pourmohammadi","year":"2011"},{"key":"b7","series-title":"Int J Biol Macromol","first-page":"212","article-title":"Chitosan-titanium dioxide-Glucantime nanoassemblies effects on promastigote and amastigote of Leishmania major","volume":"107","author":"Varshosaz","year":"2018"},{"key":"b8","series-title":"Antimicrob Agents Chemother","first-page":"1076","article-title":"Characterization of the antimonial antileishmanial agent meglumine antimonate (Glucantime)","volume":"42","author":"Roberts","year":"1998"},{"key":"b9","series-title":"J Infect Public Health","first-page":"120","article-title":"Efficacy of Glucantime for treatment of cutaneous leishmaniasis in central Iran","volume":"6","author":"Mohammadzadeh","year":"2013"},{"key":"b10","series-title":"Int J Biol Macromol","first-page":"288","article-title":"Glucantime-loaded electrospun core-shell nanofibers composed of poly (ethylene oxide)\/gelatin-poly (vinyl alcohol)\/chitosan as dressing for cutaneous leishmaniasis","volume":"163","author":"Alishahi","year":"2020"},{"key":"b11","series-title":"Drug Dev Ind Pharm","first-page":"701","article-title":"Double-walled microspheres loaded with meglumine antimoniate: preparation, characterization and in\u00a0vitro release study","volume":"40","author":"Navaei","year":"2013"},{"key":"b12","series-title":"Radiat Phys Chem","first-page":"194","article-title":"Influence of chitosan\/clay in drug delivery of Glucantime from PVP membranes","volume":"94","year":"2014"},{"key":"b13","series-title":"Drug Deliv","first-page":"564","article-title":"Permeation enhancer strategies in transdermal drug delivery","volume":"23","author":"Marwah","year":"2016"},{"key":"b14","series-title":"Sustain Chem Pharm","first-page":"37","article-title":"Lipid nanoparticles: different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery","volume":"6","author":"Ganesan","year":"2017"},{"key":"b15","series-title":"Int J Nanomedicine","first-page":"289","article-title":"Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule","volume":"9","author":"Lee","year":"2014"},{"key":"b16","series-title":"Int J Pharm","first-page":"63","article-title":"Topical transport of hydrophilic compounds using water-in-oil nanoemulsions","volume":"220","author":"Wu","year":"2001"},{"key":"b17","series-title":"Pharmacol Rep","first-page":"156","article-title":"Nanostructured lipid carriers: a potential use for skin drug delivery systems","volume":"71","author":"Czajkowska-Ko\u015bnik","year":"2019"},{"key":"b18","series-title":"Mater Today Commun","first-page":"104409","article-title":"Evaluation of vitamin D3 serum level of microemulsion based hydrogel containing Calcipotriol drug","volume":"33","author":"Ghorbanzadeh","year":"2022"},{"key":"b19","series-title":"Expert Opin Drug Deliv","first-page":"165","article-title":"Nanostructured lipid carrier-based hydrogel formulations for drug delivery: a comprehensive review","volume":"6","author":"Doktorovova","year":"2009"},{"key":"b20","series-title":"Exp Parasitol","first-page":"5","article-title":"Use of topical liposomes containing meglumine antimoniate (Glucantime) for the treatment of L. major lesion in BALB\/c mice","volume":"143","author":"Kalat","year":"2014"},{"key":"b21","series-title":"J Liposome Res","first-page":"134","article-title":"Development of liposomes loaded with anti-leishmanial drugs for the treatment of cutaneous leishmaniasis","volume":"23","author":"Momeni","year":"2013"},{"key":"b22","series-title":"Sci Rev Chem Comm","first-page":"80","article-title":"Solid lipid nanoparticles: a review","volume":"2","author":"Ekambaram","year":"2012"},{"key":"b23","series-title":"Adv Drug Deliv Rev","first-page":"83","article-title":"Solid lipid nanoparticles: production, characterization and applications","volume":"64","author":"Mehnert","year":"2012"},{"key":"b24","series-title":"Colloids Surf A Physicochem Eng Asp","first-page":"76","article-title":"Formulation and characterization of nanostructured lipid carriers containing a mixed lipids core","volume":"430","author":"Zheng","year":"2013"},{"key":"b25","series-title":"Antimicrob Resist Infect Control","first-page":"1","article-title":"Enhanced bactericidal effect of ceftriaxone drug encapsulated in nanostructured lipid carrier against gram-negative Escherichia coli bacteria: drug formulation, optimization, and cell culture study","volume":"9","author":"Ebrahimi","year":"2020"},{"key":"b26","series-title":"J Dermatolog Treat","first-page":"593","article-title":"Effects of carbomer 940 hydrogel on burn wounds: an in\u00a0vitro and in\u00a0vivo study","volume":"29","author":"Hayati","year":"2018"},{"key":"b27","series-title":"Foot","first-page":"14","article-title":"The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration","volume":"40","author":"Motawea","year":"2019"},{"key":"b28","series-title":"Colloids Surf B Biointerfaces","first-page":"393","article-title":"Formulation, clinical and histopathological assessment of microemulsion based hydrogel for UV protection of skin","volume":"179","author":"Ghorbanzadeh","year":"2019"},{"key":"b29","series-title":"Pharmaceutics","first-page":"97","article-title":"Freeze-dried lopinavir-loaded nanostructured lipid carriers for enhanced cellular uptake and bioavailability: statistical optimization, in\u00a0vitro and in\u00a0vivo evaluations","volume":"11","author":"Khan","year":"2019"},{"key":"b30","series-title":"Pharmaceutics","first-page":"531","article-title":"Development of a nanostructured lipid carrier (NLC) by a low-energy method, comparison of release kinetics and molecular dynamics simulation","volume":"13","author":"Ortiz","year":"2021"},{"key":"b31","series-title":"Bull Fac Pharm Cairo Univ","first-page":"147","article-title":"Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride","volume":"53","author":"Gaba","year":"2015"},{"key":"b32","series-title":"J Nanosci Nanotechnol","first-page":"800","article-title":"Hydrogels containing nanocapsules and nanoemulsions of tea tree oil provide antiedematogenic effect and improved skin wound healing","volume":"15","author":"Flores","year":"2015"},{"key":"b33","series-title":"Pharmaceutics","first-page":"151","article-title":"Evaluation of formulation parameters on permeation of ibuprofen from topical formulations using Strat-M\u00ae membrane","volume":"12","author":"Bolla","year":"2020"},{"key":"b34","series-title":"Glob Cardiol Sci Pract","first-page":"38","article-title":"Hydrogel scaffolds for tissue engineering: progress and challenges","volume":"2013","author":"El-Sherbiny","year":"2013"},{"key":"b35","series-title":"J Ayurveda Integr Med","first-page":"124","article-title":"Formulation and in\u00a0vitro evaluation of the topical antiageing preparation of the fruit of Benincasa hispida","volume":"2","author":"Sabale","year":"2011"},{"key":"b36","series-title":"Braz J Pharm Sci","first-page":"63","article-title":"Physical chemistry evaluation of stability, spreadability, in\u00a0vitro antioxidant, and photo-protective capacities of topical formulations containing Calendula officinalis L. leaf extract","volume":"51","author":"Deuschle","year":"2015"},{"key":"b37","series-title":"Eur J Pharm Sci","first-page":"479","article-title":"Preparation, characterization and in-vivo evaluation of microemulsions containing tamoxifen citrate anti-cancer drug","volume":"96","author":"Dehghani","year":"2017"},{"key":"b38","series-title":"Drug Dev Ind Pharm","first-page":"1619","article-title":"Preparation, characterization and in\u00a0vitro evaluation of microemulsion of raloxifene hydrochloride","volume":"43","author":"Golmohammadzadeh","year":"2017"},{"key":"b39","series-title":"Nanomedicine","first-page":"1034","article-title":"Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in\u00a0vitro and ex vivo studies","volume":"8","author":"Ara\u00fajo","year":"2012"},{"key":"b40","series-title":"Colloids Surf B Biointerfaces","first-page":"111691","article-title":"Enhanced antibacterial activity of uniform and stable chitosan nanoparticles containing metronidazole against anaerobic bacterium of Bacteroides fragilis","volume":"202","author":"Binesh","year":"2021"},{"key":"b41","series-title":"Evid Based Complement Altern Med","first-page":"149707","article-title":"In vitro and in\u00a0vivo antileishmanial effects of Pistacia khinjuk against Leishmania tropica and Leishmania major","volume":"2015","author":"Ezatpour","year":"2015"},{"key":"b42","series-title":"J Drug Deliv Sci Technol","first-page":"101232","article-title":"Formulation of topical NLCs to target macrophages for cutaneous leishmaniasis","volume":"54","author":"Riaz","year":"2019"},{"key":"b43","series-title":"Pharm Biol","first-page":"1052","article-title":"Leishmanicidal and cytotoxic activities of Nigella sativa and its active principle, thymoquinone","volume":"53","author":"Mahmoudvand","year":"2015"},{"key":"b44","series-title":"J Control Release","first-page":"735","article-title":"Enhanced skin permeation using polyarginine modified nanostructured lipid carriers","volume":"161","author":"Shah","year":"2012"},{"key":"b45","series-title":"Lab Anim","first-page":"16","article-title":"Pigmented spleens in C57BL mice","volume":"23","author":"Veninga","year":"1989"},{"key":"b46","series-title":"J Pharmacol Pharmacother","first-page":"87","article-title":"Blood sample collection in small laboratory animals","volume":"1","author":"Parasuraman","year":"2010"},{"key":"b47","series-title":"J Am Chem Soc","first-page":"866","article-title":"Synthetic glycerides. I. Preparation and melting points of glycerides of known constitution","volume":"51","author":"Averill","year":"1929"},{"key":"b48","series-title":"Carbohydr Polym","first-page":"435","article-title":"A comparative study on the efficiency of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan surface modified nanostructured lipid carrier for ophthalmic delivery of curcumin","volume":"146","author":"Li","year":"2016"},{"key":"b49","series-title":"J Am Pharm Assoc","first-page":"342","article-title":"The effect of pH variations of ointment bases on the local anesthetic activity of incorporated ethyl aminobenzoate. I. Hydrophilic ointment USP","volume":"44","author":"Bhatia","year":"1955"},{"key":"b50","series-title":"Biol Pharm Bull","first-page":"2326","article-title":"Preparation of fucoidan-chitosan hydrogel and its application as burn healing accelerator on rabbits","volume":"31","author":"Sezer","year":"2008"},{"key":"b51","series-title":"Appl Nanosci","first-page":"529","article-title":"A rapid and versatile method for solvothermal synthesis of Sb 2 O 3 nanocrystals under mild conditions","volume":"3","author":"Kaviyarasu","year":"2013"},{"key":"b52","series-title":"Indonesian J Sci Technol","first-page":"97","article-title":"How to read and interpret FTIR spectroscope of organic material","volume":"4","author":"Nandiyanto","year":"2019"},{"key":"b53","series-title":"Pharmaceutics","first-page":"262","article-title":"Quantitative structure\u2013activity relationship of enhancers of licochalcone a and glabridin release and permeation enhancement from carbomer hydrogel","volume":"14","author":"Wang","year":"2022"},{"key":"b54","series-title":"Adv Pharm Bull","first-page":"563","article-title":"Encapsulation of vitamin A palmitate in nanostructured lipid carrier (NLC)-effect of surfactant concentration on the formulation properties","volume":"4 (Suppl 2):","author":"Pezeshki","year":"2014"},{"key":"b55","series-title":"Colloids Surf B Biointerfaces","first-page":"517","article-title":"Physicochemical characterization of solid lipid nanoparticles comprised of glycerol monostearate and bile salts","volume":"172","author":"Talele","year":"2018"},{"key":"b56","series-title":"Int Forum Allergy Rhinol","first-page":"810","article-title":"Tween 80 and its derivative oleic acid promote the growth of Corynebacterium accolens and inhibit Staphylococcus aureus clinical isolates","volume":"11","author":"Menberu","year":"2021"},{"key":"b57","series-title":"Cell Biochem Funct","first-page":"197","article-title":"Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats","volume":"26","author":"Pereira","year":"2008"},{"key":"b58","series-title":"Immunobiology","first-page":"409","article-title":"Oleic acid modulation of the immune response in wound healing: a new approach for skin repair","volume":"216","author":"Cardoso","year":"2011"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/2\/article-p301.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/2\/article-p301.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/2\/article-p301.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T13:03:19Z","timestamp":1690981399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/2\/article-p301.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":58,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.23-0116","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}