{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:11:14Z","timestamp":1780528274463,"version":"3.54.1"},"reference-count":53,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Dent"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>One of the causes of congenital cleft lip\/palate abnormalities is maternal folic acid deficiency. A common issue during the first trimester is nausea, vomiting, and, in some cases, hyperemesis gravidarum, which can hinder optimal folic acid intake. The application of transdermal patches represents a significant advancement in systemic drug delivery through intact skin. This study aimed to formulate and evaluate a folic acid nanoparticle transdermal patch that effectively bypasses gastrointestinal absorption, addressing a critical need during the first trimester of pregnancy.<\/jats:p>\n                  <jats:p>The ionic gelation technique was utilized to produce folic acid nanoparticles derived from chitosan extracted from shrimp shells. Nanochitosan from shells is a natural polymer used in the encapsulation of the target active ingredient, folic acid. Characterization of nanoparticles was assessed with particle size analysis (PSA) and zeta sizing techniques, transmission electron microscope (TEM), Fourier transform infrared (FTIR), to examine a specific molecular structure and chemical bonding of the folic acid nanoparticles, and scanning electron microscope to assess its morphology. The transdermal patch was assessed for its organoleptic characteristics and various physicochemical properties. In vivo studies were conducted to evaluate skin permeation and potential irritation.<\/jats:p>\n                  <jats:p>The study successfully created a patch containing folic acid nanoparticles with an average size of 290.7\u2009nm and a zeta potential of \u221218.7\u2009mV. Organoleptic testing revealed that the patch was odorless, exhibited a clear yellow color, was flexible, was free of cracks, and maintained a moist texture. The physicochemical analyses indicated a pH of 6, an average weight variance of 0.280233\u2009\u00b1\u2009SD (0.0428345), a thickness of 0.0330\u2009\u00b1\u2009SD (0.01264), a moisture content of 37.1067%\u2009\u00b1\u2009SD (4.20015%), and a folding resistance of up to 500 folds. Cumulative permeation results showed \u223c30% absorption over 480\u2009minutes. It is noteworthy that significant irritation was observed in four of the six animal test groups.<\/jats:p>\n                  <jats:p>This study has led to the development of an innovative folate-nanoparticle transdermal patch that exhibits promising morphological characteristics. However, additional research focusing on formulation and dosage optimization is required to achieve enhanced permeation and to minimize skin irritation before initiating clinical studies.<\/jats:p>","DOI":"10.1055\/s-0046-1820074","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:49:22Z","timestamp":1780526962000},"source":"Crossref","is-referenced-by-count":0,"title":["Advanced Transdermal Patches with Folate Nanoparticles: A Breakthrough in Prenatal Supplementation"],"prefix":"10.1055","author":[{"given":"Yayun Siti","family":"Rochmah","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-857X","authenticated-orcid":false,"given":"Stefani","family":"Harumsari","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naniek","family":"Widyaningrum","sequence":"additional","affiliation":[{"name":"Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizqa","family":"Citradewi","sequence":"additional","affiliation":[{"name":"Master Program of Dental Sciences, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4331-2403","authenticated-orcid":false,"given":"Hera","family":"Septania","sequence":"additional","affiliation":[{"name":"Master Program of Dental Sciences, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8975-2055","authenticated-orcid":false,"given":"Maulida Dara","family":"Harjanti","sequence":"additional","affiliation":[{"name":"Master Program of Dental Sciences, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islamy Rahma","family":"Hutami","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-2970","authenticated-orcid":false,"given":"Sandy","family":"Christiono","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Faculty of Dentistry, Universitas Islam Sultan Agung, Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12916-021-01914-9","article-title":"Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial","volume":"19","author":"A Caffrey","year":"2021","journal-title":"BMC Med"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12916-019-1432-4","article-title":"Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial)","volume":"17","author":"H McNulty","year":"2019","journal-title":"BMC Med"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jobcr.2025.01.021","article-title":"Early cognizance of folic acid supplementation among pregnant women in the prevention of cleft lip and palate - a questionnaire study","volume":"15","author":"K P Nakkeeran","year":"2025","journal-title":"J Oral Biol Craniofac Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1186\/s13063-020-04320-3","article-title":"Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? 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