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The developed TZN-PN exhibited relatively high EE% (75.78\u201385.45%), a VS ranging between (348\u2013559 nm), and a ZP (\u221226.47 to \u221259.64). In vitro release profiles revealed sustained release of TZN from the optimized TZN-PN, compared to free drug up to 24 h. In vivo rotarod study revealed that the elevation in coordination was in the following order: normal control &lt; free TZN &lt; market product &lt; TZN-PN (F6). Moreover, the optimized TZN-PN exhibited significant elevated coordination activity by 39% and 26% compared to control group and market product group, respectively. This was accompanied with an elevation in both GABA and EAAT2 serum levels. Thus, it could be concluded that encapsulation of TZN in the provesicular nanosystem proniosomes has enhanced the anti-nociceptive effect of the drug and consequently its therapeutic activity.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s13346-022-01217-3","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T20:13:55Z","timestamp":1659644035000},"page":"580-592","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Formulation of tizanidine hydrochloride\u2013loaded provesicular system for improved oral delivery and therapeutic activity employing a 23 full factorial design"],"prefix":"10.1007","volume":"13","author":[{"given":"Amira Mohamed","family":"Mohsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeer Ahmed","family":"El-Hashemy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-5330","authenticated-orcid":false,"given":"Asmaa Badawy","family":"Darwish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"1217_CR1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1017\/CBO9780511544866.005","volume-title":"Upper Motor Neurone Syndrome and Spasticity: Clinical Management and Neurophysiology","author":"R Boyd","year":"2008","unstructured":"Boyd R, Ada L. 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