{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:51:10Z","timestamp":1776199870701,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w\/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w\/w of Smix (Labrasol and Transcutol HP, and 40% w\/w of water resulting in a globule size of 124.6 \u00b1 3.52 nm with low polydispersity index (PDI) (0.212 \u00b1 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC0\u2013t24 (18.63 \u00b1 1.33 h \u00d7 \u00b5g\/g) in the brain by approximately 4.3-fold than oral ME (4.30 \u00b1 0.92 h \u00d7 \u00b5g\/g) and 7.7-fold than intravenous drug solutions (2.40 \u00b1 0.36 h \u00d7 \u00b5g\/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.<\/jats:p>","DOI":"10.3390\/pharmaceutics14050978","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:08:58Z","timestamp":1651475338000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics"],"prefix":"10.3390","volume":"14","author":[{"given":"Sravanthi","family":"Pailla","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-7698","authenticated-orcid":false,"given":"Sunitha","family":"Sampathi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India"},{"name":"GITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad 502329, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-2036","authenticated-orcid":false,"given":"Vijayabhaskarreddy","family":"Junnuthula","sequence":"additional","affiliation":[{"name":"Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00790 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sravya","family":"Maddukuri","sequence":"additional","affiliation":[{"name":"GITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad 502329, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-7077","authenticated-orcid":false,"given":"Sujatha","family":"Dodoala","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati 517502, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-1651","authenticated-orcid":false,"given":"Sathish","family":"Dyawanapelly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science and Technology, Institute of Chemical Technology, Mumbai 400019, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"St\u0119pnicki, P., Kondej, M., and Kaczor, A.A. 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