{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:50:35Z","timestamp":1791237035196,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573357"],"award-info":[{"award-number":["81573357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Technologies Research and Development Program for New Drugs of China","award":["2018ZX09721003-007"],"award-info":[{"award-number":["2018ZX09721003-007"]}]},{"name":"National Key Technologies Research and Development Program for New Drugs of China","award":["2018ZX09J18107"],"award-info":[{"award-number":["2018ZX09J18107"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>\u03b1-Conotoxin GeXIVA[1,2] is a highly potent and selective antagonist of the \u03b19\u03b110 nicotinic acetylcholine receptor (nAChR) subtype. It has the advantages of strong efficacy, no tolerance, and no effect on motor function, which has been expected help patients with neuropathic pain. However, drug development for clinical use is severely limited owing to its instability. Lyophilization is applied as the most preferred method to solve this problem. The prepared lyophilized powder is characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR). Molecular simulation is also used to explore the internal distribution and forces formed in the system. The analgesic effect on paclitaxel-induced neuropathic pain following single and 14-day repeated administrations are evaluated by the von Frey test and the tail-flick test. Trehalose combined with mannitol in a ratio of 1:1 is employed as the excipients in the determined formulation, where trehalose acts as the stabilizer and mannitol acts as the bulking agent, according to the results of DSC, PXRD, and FTIR. Both GeXIVA[1,2] (API) and GeXIVA[1,2] lyophilized powder (formulation) could produce stable analgesic effect. These results indicated that GeXIVA[1,2] lyophilized powder could improve the stability and provide an effective strategy to push it into clinical use as a new analgesic drug.<\/jats:p>","DOI":"10.3390\/md19030121","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T02:08:17Z","timestamp":1614305297000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Lyophilization Serves as an Effective Strategy for Drug Development of the \u03b19\u03b110 Nicotinic Acetylcholine Receptor Antagonist \u03b1-Conotoxin GeXIVA[1,2]"],"prefix":"10.3390","volume":"19","author":[{"given":"Zhiguo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27th Taiping Road, Haidian District, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"f7656","DOI":"10.1136\/bmj.f7656","article-title":"Neuropathic pain: Mechanisms and their clinical implications","volume":"348","author":"Cohen","year":"2014","journal-title":"BMJ"},{"key":"ref_2","first-page":"1589","article-title":"Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects","volume":"1288","author":"Furlan","year":"2001","journal-title":"CMAJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1001\/jama.2016.1464","article-title":"CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016","volume":"315","author":"Dowell","year":"2016","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1097\/00000542-200603000-00025","article-title":"Opioid-induced hyperalgesia: A qualitative systematic review","volume":"104","author":"Angst","year":"2006","journal-title":"Anesthesiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.7326\/M14-2559","article-title":"The effectiveness and risks of long-term opioid therapy for chronic pain: A systematic review for a National Institutes of Health Pathways to Prevention Workshop","volume":"162","author":"Chou","year":"2015","journal-title":"Ann. 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