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PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and <jats:italic>in vitro<\/jats:italic> release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7\u2009\u00b1\u20090.15\u2009\u00b5g quercetin equivalents and phenolic content of 180.8\u2009\u00b1\u20090.11\u2009\u00b5g gallic acid equivalents\/mg. Multilamellar niosomes of 176\u2013333\u2009nm displayed entrapment efficiency of 91\u2009\u00b1\u20090.48%, PDI of 0.676 and zeta potential of \u22124.99. <jats:italic>In vitro<\/jats:italic> release after 8\u2009h from niosomal dispersion and films were 64.05% and 29.09\u2009\u00b1\u20090.13% respectively. Clinical results revealed duration of film adherence from 2\u20134\u2009h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4\u20135\u2009h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.<\/jats:p>","DOI":"10.1038\/s41598-018-37157-7","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T15:44:53Z","timestamp":1545234293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Propolis-based niosomes as oromuco-adhesive films: A randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers"],"prefix":"10.1038","volume":"8","author":[{"given":"Mona G.","family":"Arafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Ghalwash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina M.","family":"El-Kersh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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