{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:42:08Z","timestamp":1788946928142,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Leishmaniasis, remains a serious health problem in many developing countries with thousands of new cases recorded annually. Novel therapies are required as existing treatment regimens are limited by their high cost, high toxicity, increased parasite resistance, patient\u2019s intolerance, and invasive means of long-duration administration. With several studies reporting the anti-leishmaniasis promise of medicinal plants, interest in plants and herbal drugs is attracting much attention worldwide. In this pilot study, we analysed extracts of Linum usitatissimum seeds (LU) to identify essential phytochemicals and test their activity against cutaneous leishmaniasis both in-vitro and in-vivo. We performed phytochemical screening of LU seeds extract as well as its in-vitro leishmanicidal and anti-amastigote assays. Water-in-oil cream containing 10% LU crude extract (10 mg\/mL) was then prepared. The stability of the cream was evaluated for 28 days at 8 \u00b0C, 25 \u00b0C and 40 \u00b0C. In-vivo efficacy and safety of the cream was performed in 26 patients with cutaneous leishmaniasis who agreed to participate voluntarily in the study. The active treatment period lasted for 3 weeks, while the follow-up period was extended to 4 months. During the active study period, images of skin lesions were taken before and after treatment. Analyses of LU seeds extract confirmed the presence of terpenoids, flavonoids, tannins, alkaloids, and polyphenols. In-vitro studies showed significant activity against promastigote and intracellular amastigote forms of Leishmaniamajor. The cream was pharmaceutically stable, although some minor changes were noticed in relation to its physical characteristics. In-vivo assessment of the cream showed a 69.23% cure rate with no side effects, allergy, or irritation. We conclude that our newly developed water in oil cream containing 10% LU seeds extract could be an effective and safe topical anti-leishmanial medication for patients with CL.<\/jats:p>","DOI":"10.3390\/antibiotics11040432","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fabrication and Evaluation of W\/O Emulsion Loaded with Linum usitatissimum Seeds Extract for Anti-Leishmaniasis Efficacy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4920-1770","authenticated-orcid":false,"given":"Barkat Ali","family":"Khan","sequence":"first","affiliation":[{"name":"Drug Delivery and Cosmetics Lab (DDCL), Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumera","family":"Faiz","sequence":"additional","affiliation":[{"name":"Drug Delivery and Cosmetics Lab (DDCL), Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6079-6571","authenticated-orcid":false,"given":"Muhammad Khalid","family":"Khan","sequence":"additional","affiliation":[{"name":"Drug Delivery and Cosmetics Lab (DDCL), Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-7322","authenticated-orcid":false,"given":"Farid","family":"Menaa","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine and Dermatology, California Innovation Corporation, San Diego, CA 92113, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5204-6885","authenticated-orcid":false,"given":"Neli-Kinga","family":"Olah","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Vasile Goldi\u0219 Western University, 310045 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosif","family":"Almoshari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawaher Abdullah","family":"Alamoudi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Almawash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 15273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: A review","volume":"6","author":"Arenas","year":"2017","journal-title":"F1000 Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s40257-015-0114-z","article-title":"Cutaneous leishmaniasis: Recent developments in diagnosis and management","volume":"16","author":"Reedijk","year":"2015","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.apjtm.2017.07.015","article-title":"First report on molecular characterization of Leishmania species from cutaneous leishmaniasi spatients in southern Khyber Pakhtunkhwa Province of Pakistan","volume":"10","author":"Hussain","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.26719\/2014.20.4.217","article-title":"Small bite, big threat: World Health Day 2014","volume":"20","author":"Savioli","year":"2014","journal-title":"East. Mediterr. Health J. Rev. St. M\u00e9diterran\u00e9e Orient."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1080\/14756366.2021.1969385","article-title":"Pyrrolidine-based 3-deoxysphingosylphosphorylcholine analogs as possible candidates against neglected tropical diseases (NTDs): Identification of hit compounds towards development of potential treatment of Leishmania donovani","volume":"36","author":"Hassan","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hodiamont, C.J., Kager, P.A., Bart, A., de Vries, H.J., van Thiel, P.P., Leenstra, T., de Vries, P.J., van Vugt, M., Grobusch, M.P., and van Gool, T. (2014). Species-directedtherapy for leishmaniasisin returning travellers: Comprehensive guide. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002832"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fmicb.2012.00283","article-title":"Conventional therapy and promising plant-derived compounds against trypanosomatid parasites","volume":"3","author":"Alviano","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Blum, J., Neumayr, A., and Lockwood, D. (2018). Treatment of Tegumentary Forms of Leishmaniasis. The Leishmaniases: Old Neglected Tropical Diseases, Springer.","DOI":"10.1007\/978-3-319-72386-0_9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fimmu.2014.00193","article-title":"Exploring the role of medicinal plant- based immunomodulators for effective therapy of leishmaniasis","volume":"5","author":"Chouhan","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_10","first-page":"157","article-title":"Natural products in antileishmanial drug discovery: A review","volume":"3","author":"Adebayo","year":"2013","journal-title":"J. Asian Sci. Res."},{"key":"ref_11","first-page":"1","article-title":"Plant-derived compounds in treatment of leishmaniasis","volume":"16","author":"Oryan","year":"2015","journal-title":"Iran. J. Vet. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exppara.2014.03.002","article-title":"Activity of olive leaf extracts against the promastigote stage of Leishmania species and their correlation with the antioxidant activity","volume":"141","author":"Sifaoui","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1051\/parasite\/2014016","article-title":"Antileishmanial activity of a mixture of Tridaxprocumbens and Allium sativum in mice","volume":"21","year":"2014","journal-title":"Parasite"},{"key":"ref_14","first-page":"349","article-title":"The effect of vitis vinifera L. leaves extract on leishmania infantum","volume":"12","author":"Mansour","year":"2013","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1590\/S1984-29612012000300002","article-title":"In vitro efficacy of Coriandrum sativum, Lippia sidoides and Copaifera reticulata against Leishmania chagasi","volume":"21","author":"Rondon","year":"2012","journal-title":"Rev. Bras. Parasitol. Vet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exppara.2013.12.006","article-title":"Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis","volume":"137","author":"Sachdeva","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.parint.2013.09.016","article-title":"Asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo","volume":"63","author":"Sachdeva","year":"2014","journal-title":"Parasitol. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.amsu.2017.07.057","article-title":"Medicinal plants with promising antileishmanial activity in Iran: A systematic revie and meta-analysis","volume":"21","author":"Soosaraei","year":"2017","journal-title":"Ann. Med. Surg."},{"key":"ref_19","first-page":"9","article-title":"Antileishmanial activity of Aloe secundiflora plant extracts against Leishmania major","volume":"13","author":"Ogeto","year":"2013","journal-title":"Adv. Life Sci. Technol."},{"key":"ref_20","first-page":"42","article-title":"Comparative efficacy of Aloe vera and Tamarixaphylla against cutaneous leishmaniasis","volume":"2","author":"Iqbal","year":"2012","journal-title":"Int. J. Basic Med. Sci. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15931","DOI":"10.1039\/C7RA02070H","article-title":"Differential effects of in vitro cultures of Linum usitatissimum L. (Flax) on biosynthesis, stability, antibacterial and antileishmanial activities of zinc oxide nanoparticles: A mechanistic approach","volume":"7","author":"Abbasi","year":"2017","journal-title":"RSC Adv."},{"key":"ref_22","first-page":"897","article-title":"Detection of the morphological and genetic effect of chloroformic flax seed extract on the Leishmania tropica","volume":"14","author":"Abed","year":"2020","journal-title":"Drug Invent. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1049\/iet-nbt.2016.0106","article-title":"Biosynthesis and characterisation of nano-silica as potential system for carrying streptomycin at nano-scale drug delivery","volume":"11","author":"Jabeen","year":"2017","journal-title":"IET Nanobiotechnol."},{"key":"ref_24","first-page":"342","article-title":"Formulation and pharmaceutical evaluation of a W\/O emulsion of Hippo phaerhamnoides","volume":"6","author":"Barkat","year":"2010","journal-title":"J. Pharm. Res."},{"key":"ref_25","first-page":"218","article-title":"Phytochemical screening of flaxseed (Linum usitatissimum L.)","volume":"5","author":"Sarah","year":"2016","journal-title":"Int. J. Sci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0378-8741(01)00346-4","article-title":"Antiprotozoal activities of Colombian plants","volume":"78","author":"Weniger","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","first-page":"1934578X211031148","article-title":"Antileishmanial Potential of Berberine Alkaloids from Berberis glaucocarpa Roots: Molecular Docking Suggests Relevant Leishmania Protein Targets","volume":"16","author":"Alamzeb","year":"2021","journal-title":"Nat. Prod. Commun."},{"key":"ref_28","unstructured":"Sofowora, A. (1993). Medicinal Plants and Traditional Medicinal in Africa, Spectrum Books Ltd.. [2nd ed.]. Screening Plants for Bioactive Agents."},{"key":"ref_29","unstructured":"Trease, G.E., and Evans, W.C. (2002). Pharmacognosy, Saunders Publishers. [15th ed.]."},{"key":"ref_30","first-page":"293","article-title":"Effect of solvents extraction on total phenolics and antioxidant activity of extracts from flaxseed (Linum usitatissimum L.)","volume":"11","author":"Anwar","year":"2012","journal-title":"Acta Sci. Pol. Technol. Aliment."},{"key":"ref_31","first-page":"236","article-title":"Formulation development and pharmaceutical evaluation of a W\/O emulsion of Coleus extract","volume":"45","author":"Akhtar","year":"2011","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/ics.12184","article-title":"Formulation and evaluation on human skin of a water-in-oil emulsion containing Muscat hamburg black grape seed extract","volume":"37","author":"Sharif","year":"2015","journal-title":"Int. J. Cosmet. Sci."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/4\/432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:41:57Z","timestamp":1760136117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/4\/432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,23]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["antibiotics11040432"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11040432","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,23]]}}}