{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:23:46Z","timestamp":1792113826738,"version":"4.4.0"},"reference-count":89,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008693","name":"Gulf Medical University","doi-asserted-by":"publisher","award":["GMU\/COP\/GR\/2024-Sept-07"],"award-info":[{"award-number":["GMU\/COP\/GR\/2024-Sept-07"]}],"id":[{"id":"10.13039\/100008693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant\u2013co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (\u221266.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p &lt; 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101355","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:54:41Z","timestamp":1760968481000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Injectable In Situ Thermoreversible Gel Depot System of Lidocaine Nanoemulsion for Prolonged Anesthetic Activity in Dental and Operative Procedures"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-6673","authenticated-orcid":false,"given":"Shery","family":"Jacob","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3307-0050","authenticated-orcid":false,"given":"Fathima Sheik","family":"Kather","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-2073","authenticated-orcid":false,"given":"Shakta Mani","family":"Satyam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-5879","authenticated-orcid":false,"given":"Sai H. S.","family":"Boddu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firas","family":"Assaf","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8897-1495","authenticated-orcid":false,"given":"Tasnem H. Abdelfattah","family":"Allam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-8669","authenticated-orcid":false,"given":"Anroop B.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shipton, E.A. (2012). New formulations of local anaesthetics-part I. Anesthesiol. Res. Pract., 2012.","DOI":"10.1155\/2012\/546409"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shipton, E.A. (2012). New delivery systems for local anaesthetics-part 2. Anesthesiol. Res. 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