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Res."],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oral ulcerative mucositis (OUM) is a common painful disease that affects oral functions, such as eating or speaking leading to a low quality of life. This study aims to develop a novel strategy for relieving pain associated with OUM by using local anesthetics. Here, a hybrid dissolving microneedle patch integrated with lidocaine (Lido)-encapsulated invasomes (modified liposomes containing terpenes as penetration enhancers) depots are introduced for sustained Lido delivery, reduced dosing frequency, and improved patient compliance. Different Lido-loaded invasomes formulations were developed using design expert\n                    <jats:sup>\u00ae<\/jats:sup>\n                    software to study the effects of different type terpenes (Limonene, Cineole, Camphor) and their concentration using a thin-film hydration approach. Dissolving microneedle (MN) patches made of sodium alginate (SA), Glycerol and polyvinyl alcohol (PVA) via the casting method. Optimized invasomes formulations containing cineole exhibited excellent stability, a high entrapment efficiency of 83.5%, and a nanoscale size of approximately 295\u00a0nm. The incorporation of SA\/PVA with 1% glycerin MNs resulted in effective mucosal penetration, rapid dissolution within 10\u00a0min, and significant mechanical strength. Research conducted in-vitro and ex-vivo demonstrated enhanced permeation and a significant increase in lidocaine release, achieving 95% within 24\u00a0h. In-vivo evaluations demonstrated substantial pain relief, reduced inflammation (evidenced by decreased TNF-\u03b1 and NF-\u03baB levels), enhanced anti-inflammatory IL-10 expression, and modulation of angiogenesis via VEGF downregulation, leading to accelerated mouth healing with complete epithelial restoration. This hybrid system significantly improves drug delivery and patient comfort by aiding in biocompatibility, Mucoadhesion, and healing. This innovative system transcends traditional anesthetic administration, providing a painless and targeted therapeutic platform that improves OUM management.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13346-025-01915-8","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T18:29:10Z","timestamp":1752776950000},"page":"635-660","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Innovate sodium alginate microneedle patches integrated with soft lidocaine invasomes: advanced strategies for oral ulcerative mucositis treatment via TNF-\u03b1\/NF-\u03baB pathways"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-2288","authenticated-orcid":false,"given":"Sammar Fathy","family":"Elhabal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa Saeed","family":"Farahat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud H.","family":"Teaima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla A.","family":"Elzohairy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Nabarawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"1915_CR1","doi-asserted-by":"crossref","unstructured":"Song J, Geng Z, Luan X, Zhang D, Wang Q, Pan L, et al. Construction of natural hydrogels consisting of oxidized dextran, quaternized chitosan and cuttlefish ink nanoparticles for treating diabetic oral ulcers. Int J Biol Macromol [Internet]. 2024 [cited 2025 Apr 5];283:137737. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/39551299","DOI":"10.1016\/j.ijbiomac.2024.137737"},{"key":"1915_CR2","doi-asserted-by":"crossref","unstructured":"Cheng H, Tian G, Liu H, Bai D, Zhang Y, Wang Q, et al. A molybdenum sulfide based nitric oxide controlled release oral gel for rapid healing of oral mucosal ulcers. J Colloid Interface Sci [Internet]. 2025 [cited 2025 Apr 3];678:560\u201371. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/39214008\/","DOI":"10.1016\/j.jcis.2024.08.210"},{"key":"1915_CR3","doi-asserted-by":"crossref","unstructured":"Elhabal SF, Faheem AM, Hababeh S, Nelson J, et al. Augmented marshmallow extract lipid nanoparticles with clove oil embedded in collagen sponge for ultimate antimicrobial healing of diabetic mouth ulcer. Pharm. 2025;17:611. [cited 2025 May 7]. Available from: https:\/\/www.mdpi.com\/1999-4923\/17\/5\/611\/htm","DOI":"10.3390\/pharmaceutics17050611"},{"key":"1915_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.141609","volume":"306","author":"X Fang","year":"2025","unstructured":"Fang X, Chen X, Dong W, Ye F. A poly(tannic acid) particle-supported \u03b2-glucan\/chitosan hydrogel for managing oral ulcers in diabetes. Int J Biol Macromol. 2025;306: 141609.","journal-title":"Int J Biol Macromol"},{"key":"1915_CR5","doi-asserted-by":"crossref","unstructured":"Zheng Y, Zhuang Z, Zhou R, Zheng L, Li C, Zhou R, et al. Next-Generation Oral Ulcer Management: Integrating Cold Atmospheric Plasma (CAP) with Nanogel-Based Pharmaceuticals for Inflammation Regulation. Adv Healthc Mater [Internet]. 2025 [cited 2025 Apr 3];14. 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