{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:04:59Z","timestamp":1791072299183,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The organoarsenical arsthinol was used in the 1950s in the treatment of amoebiasis and yaws and was considered as \u2018highly tolerated\u2019. The aim of this work was to study its anti-leukaemic activity and to develop nanosuspensions of the drug, thereby limiting brain concentrations and the risk of encephalopathy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Arsthinol nanosuspensions were produced by high-pressure homogenization. The anti-leukaemic activity was assessed on NB4 acute promyelocytic leukaemia cells (vs solutions of arsthinol, As2O3 and melarsoprol). In addition, a pharmacokinetics study was performed to compare the nanosuspensions and the solution of arsthinol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Arsthinol induced growth inhibition of NB4 cells at lower concentration (IC50 (concentration inhibiting growth by 50%) = 0.78 \u00b1 0.08 \u03bcmol\/l after 24 h) than As2O3 (IC50 = 1.60 \u00b1 0.23 \u03bcmol\/l after 24 h) or melarsoprol (IC50 = 1.44 \u00b1 0.08 \u03bcmol\/l after 24 h). When formulated as nanosuspension, arsthinol remained cytotoxic (IC50 = 1.33 \u00b1 0.30 \u03bcmol\/l after 24 h). This formulation also reduced the drug's access to the brain (Cmax = 0.03 \u03bcmol\/g) whereas bone marrow concentrations remained very high (Cmax = 2 \u03bcmol\/g).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nanosuspensions of arsthinol could be proposed for further studies in the treatment of acute promyelocytic leukaemia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1211\/jpp.61.10.0004","type":"journal-article","created":{"date-parts":[[2010,10,14]],"date-time":"2010-10-14T13:10:14Z","timestamp":1287061814000},"page":"1295-1301","source":"Crossref","is-referenced-by-count":7,"title":["Arsthinol nanosuspensions: pharmacokinetics and anti-leukaemic activity on NB4 promyelocytic leukaemia cells"],"prefix":"10.1093","volume":"61","author":[{"given":"Imane","family":"Ajana","sequence":"first","affiliation":[{"name":"EA 3452 \u2018Cibles th\u00e9rapeutiques formulation et expertise pr\u00e9clinique du m\u00e9dicament\u2019, Nancy Universit\u00e9 , Nancy,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Astier","sequence":"additional","affiliation":[{"name":"EA 3452 \u2018Cibles th\u00e9rapeutiques formulation et expertise pr\u00e9clinique du m\u00e9dicament\u2019, Nancy Universit\u00e9 , Nancy,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Gibaud","sequence":"additional","affiliation":[{"name":"EA 3452 \u2018Cibles th\u00e9rapeutiques formulation et expertise pr\u00e9clinique du m\u00e9dicament\u2019, Nancy Universit\u00e9 , Nancy,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,1]]},"reference":[{"key":"2024103109371935600_cit1","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1182\/blood.V89.9.3354","article-title":"Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients","volume":"89","author":"Shen","year":"1997","journal-title":"Blood"},{"key":"2024103109371935600_cit2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3181\/00379727-65-15902","article-title":"Effect of BAL on trichomona-cidal activity of some organic arsenicals","volume":"65","author":"Friedheim","year":"1947","journal-title":"Proc Soc Exp Biol Med"},{"key":"2024103109371935600_cit3","volume-title":"Heterocyclic metal and sulfur organic compounds","author":"Friedheim","year":"1953"},{"key":"2024103109371935600_cit4","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0140-6736(00)02141-3","article-title":"Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial","volume":"355","author":"Burri","year":"2000","journal-title":"Lancet"},{"key":"2024103109371935600_cit5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000239130","article-title":"Pharmacokinetic properties of the trypanocidal drug melarsoprol","volume":"39","author":"Burri","year":"1993","journal-title":"Chemotherapy"},{"key":"2024103109371935600_cit6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1001\/jama.1956.02960400018005","article-title":"Intestinal amebiasis: incidence, symptoms, and treatment with arsthinol (Balarsen)","volume":"160","author":"Brown","year":"1956","journal-title":"JAMA"},{"key":"2024103109371935600_cit7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1159\/000256212","article-title":"Arsthinol (Balarsen) in 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