{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:52:12Z","timestamp":1790077932249,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid\u2010based nanovesicles for the co\u2010delivery of buprenorphine and bupivacaine to efficiently target skin\u2010concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in\u2010vitro drug release of vesicles were characterized. Ex\u2010vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full\u2010thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex\u2010vivo fluorescent dye tracking. Estimation of in\u2010vivo pain responses by the tail\u2010flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug\u2010free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10\u2009min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex\u2010vivo and in\u2010vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.<\/jats:p>","DOI":"10.1111\/exd.14850","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T04:16:37Z","timestamp":1686197797000},"page":"1459-1467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nano\u2010invasomes for simultaneous topical delivery of buprenorphine and bupivacaine for dermal analgesia"],"prefix":"10.1111","volume":"32","author":[{"given":"Soraya","family":"Babaie","sequence":"first","affiliation":[{"name":"Physical Medicine and Rehabilitation Research Center, Aging Research Institute Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Charkhpour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Kouhsoltani","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology, Faculty of Dentistry Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Hamishehkar","sequence":"additional","affiliation":[{"name":"Drug Applied Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-6000","authenticated-orcid":false,"given":"Ana Cl\u00e1udia","family":"Paiva\u2010Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra University of Coimbra  Coimbra Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra 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