{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:38:58Z","timestamp":1790386738003,"version":"4.1.0"},"reference-count":75,"publisher":"Bentham Science Publishers Ltd.","issue":"4","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CDD"],"published-print":{"date-parts":[[2020,6,27]]},"abstract":"<jats:sec>\n<jats:title>Background::<\/jats:title>\n<jats:p>Recently we developed a scalable scheme of synthesis of melphalan ester conjugate\nwith 1,2-dioleoyl-sn-glycerol (MlphDG) and a protocol for the fabrication of its lyophilized\nliposomal formulation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>Herein we compared this new convenient in use formulation of MlphDG with parent drug\nAlkeran\u00ae in rats concerning several toxicological parameters and evaluated its antitumor efficacy in the\nmodel of breast cancer in mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Method:<\/jats:title>\n<jats:p>Liposomes of approximately 100 nm in diameter, consisting of egg phosphatidylcholine, soybean\nphosphatidylinositol, and MlphDG, or placebo liposomes without the drug were produced by extrusion\nand lyophilized. Alkeran\u00ae or liposomes recovered by the addition of water were injected into the\ntail vein of animals. Clinical examination of rats consisted of detailed inspection of the behavior, general\nstatus, and hematological parameters. Mice with transplanted breast cancer WNT-1 were subjected\nto multiple treatments with the drugs; tumor growth inhibition was assessed, together with cellular immunity\nparameters.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>Liposomes showed approximately two times lower acute toxicity and better tolerability than\nAlkeran\u00ae in terms of behavioral criteria. The toxic effects of liposomes on hemopoiesis were manifested\nat higher doses than in the case of Alkeran\u00ae, proportionally to the difference in LD50 values. The formulation\ninhibited tumor growth significantly more effectively than Alkeran\u00ae, delaying the start of the\nexponential growth phase and exhibiting no additional toxic effects toward bone marrow.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p> Lower toxicity of the liposomal formulation of MlphDG promises improved quality of life\nfor cancer patients in need of treatment with melphalan. Presumably, the list of indications for melphalan\ntherapy could be extended.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1567201817666200214105357","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T13:26:06Z","timestamp":1581686766000},"page":"312-323","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Liposomal Formulation of a Melphalan Lipophilic Prodrug: Studies of Acute Toxicity, Tolerability, and Antitumor Efficacy"],"prefix":"10.2174","volume":"17","author":[{"given":"Daria","family":"Tretiakova","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Svirshchevskaya","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Onishchenko","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-6183","authenticated-orcid":true,"given":"Anna","family":"Alekseeva","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Boldyrev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-7763","authenticated-orcid":true,"given":"Roman","family":"Kamyshinsky","sequence":"additional","affiliation":[{"name":"National Research Center \"Kurchatov Institute\", Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Natykan","sequence":"additional","affiliation":[{"name":"Drugs Technology Ltd., Khimki, \u041coscow Region, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Lokhmotov","sequence":"additional","affiliation":[{"name":"Drugs Technology Ltd., Khimki, \u041coscow Region, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Arantseva","sequence":"additional","affiliation":[{"name":"Drugs Technology Ltd., Khimki, \u041coscow Region, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-0582","authenticated-orcid":true,"given":"Dmitry","family":"Shobolov","sequence":"additional","affiliation":[{"name":"Drugs Technology Ltd., Khimki, \u041coscow Region, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vodovozova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","first-page":"405","author":"Teicher B.A.","year":"1997","unstructured":"Teicher B.A.;  Antitumor alkylating agents cancer principals and practice of oncology; De Vita, VT; Hellman, S 1997,405-418","journal-title":"Antitumor alkylating agents cancer principals and practice of oncology; De Vita, VT; Hellman, S"},{"key":"ref=2","doi-asserted-by":"publisher","first-page":"695","DOI":"10.2174\/157018006778631893","volume":"10","author":"Wickstr\u00f6m M.","year":"2006","unstructured":"Wickstr\u00f6m M.; L\u00f6vborg H.; Gullbo J.; Future prospects for old chemotherapeutic drugs in the target-specific era; pharmaceutics, combinations, co-drugs and prodrugs with melphalan as an example. 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