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Soc. open sci."],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>\n                    Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (\u221226.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal\/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG.\n                  <\/jats:p>","DOI":"10.1098\/rsos.220428","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T03:15:25Z","timestamp":1664939725000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":49,"title":["Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis"],"prefix":"10.1098","volume":"9","author":[{"given":"Husna","family":"Khalid","sequence":"first","affiliation":[{"name":"Nanomedicine Research Group, Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"},{"name":"Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibgha","family":"Batool","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Group, Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"},{"name":"Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-4897","authenticated-orcid":true,"given":"Fakhar ud","family":"Din","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Group, Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"},{"name":"Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gul Majid","family":"Khan","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Group, Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"},{"name":"Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan"},{"name":"Islamia College University, Peshawar, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5OB00563A"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.2012.701204"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.120109"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18671-1"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-022-02384-9"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2022.01.010"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/646932"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00853-0"},{"key":"e_1_3_7_10_2","unstructured":"World Health Organization. 2010 WHO technical report series. 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