{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:38Z","timestamp":1787015678728,"version":"build-2736575974"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Innovation Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Mefloquine (MQ) is an antimalarial drug with high efficacy, often used in the treatment and chemoprophylaxis of malaria. However, it has low solubility in water, a long elimination half-life (4 days), and is neurotoxic, which leads to unwanted side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated a lipid-based drug delivery system, Pheroid vesicles, in combination with MQ (Pheroid MQ), to promote future clinical use. MQ was incorporated into Pheroid vesicles and the formulations characterized. The formulations were evaluated in terms of in-vitro efficacy and toxicity. In-vivo bioavailability studies were conducted in C57 BL6 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>The vesicles incorporated MQ with \u223c63% entrapment efficiency. The IC50 values of MQ after 48-h incubation in chloroquine-resistant (RSA11) and chloroquine sensitive (3D7) strains, were reduced by \u223c50% and \u223c30% respectively. In-vivo bioavailability study revealed no change in the pharmacokinetic parameters of MQ, and the incorporation of the drug in Pheroid vesicles reduced the in-vitro haemolytic activity by \u223c75%. Furthermore, the cytotoxicity against human neuroblastoma cells (SH-SY5Y) of the free drug was reduced by \u223c64% with Pheroid MQ.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pheroid vesicles may therefore decrease the toxicity of MQ and thereby improve its therapeutic index, a strategy that may provide an effective alternative for malaria chemoprophylaxis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jphp.12147","type":"journal-article","created":{"date-parts":[[2013,10,13]],"date-time":"2013-10-13T23:02:39Z","timestamp":1381705359000},"page":"14-22","source":"Crossref","is-referenced-by-count":11,"title":["Formulation and evaluation of Pheroid vesicles containing mefloquine for the treatment of malaria"],"prefix":"10.1093","volume":"66","author":[{"given":"Lissinda H","family":"du Plessis","sequence":"first","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrizaan","family":"Helena","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Este","family":"van Huysteen","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awie F","family":"Kotz\u00e9","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2024103109155071200_jphp12147-cit-0001","volume-title":"World Malaria Report","author":"World Health Organization","year":"2011"},{"key":"2024103109155071200_jphp12147-cit-0002","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.pt.2012.08.002","article-title":"PfCRT and its role in antimalarial drug resistance","volume":"28","author":"Ecker","year":"2012","journal-title":"Trends Parasitol"},{"key":"2024103109155071200_jphp12147-cit-0003","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1475-2875-12-68","article-title":"The story of artesunate-mefloquine (ASMQ), innovative partnerships in drug development: case study","volume":"12","author":"Wells","year":"2013","journal-title":"Malar J"},{"key":"2024103109155071200_jphp12147-cit-0004","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1473-3099(10)70187-0","article-title":"Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial","volume":"10","author":"Smithuis","year":"2010","journal-title":"Lancet Infect Dis"},{"key":"2024103109155071200_jphp12147-cit-0005","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.trstmh.2005.02.007","article-title":"Efficacy of chloroquine + sulfadoxine \u2013 pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh","volume":"99","author":"Van den Broek","year":"2005","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2024103109155071200_jphp12147-cit-0006","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1475-2875-12-71","article-title":"Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids","volume":"12","author":"Lombard","year":"2013","journal-title":"Malar J"},{"key":"2024103109155071200_jphp12147-cit-0007","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0378-5173(94)90157-0","article-title":"Preparation, characterization and in vivo activity of mefloquine submicron emulsions","volume":"110","author":"Mbela","year":"1994","journal-title":"Int J Pharm"},{"key":"2024103109155071200_jphp12147-cit-0008","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1111\/j.2042-7158.1998.tb03337.x","article-title":"Submicron oil-in-water emulsion formulations for mefloquine and halofantrine: effect of electric-charge inducers on antimalarial activity in mice","volume":"50","author":"Mbela","year":"1998","journal-title":"J Pharm Pharmacol"},{"key":"2024103109155071200_jphp12147-cit-0009","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.ejps.2010.05.007","article-title":"Artemether-loaded lipid nanoparticles produced by modified thin-film hydration: pharmacokinetics, toxicological and in vivo anti-malarial activity","volume":"40","author":"Aditya","year":"2010","journal-title":"Eur J Pharm Sci"},{"key":"2024103109155071200_jphp12147-cit-0010","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijpharm.2007.06.035","article-title":"Formulation, antimalarial activity and biodistribution of oral lipid nanoemulsion of primaquine","volume":"347","author":"Singh","year":"2008","journal-title":"Int J Pharm"},{"key":"2024103109155071200_jphp12147-cit-0011","volume-title":"Field Application of in Vitro Assays for the Sensitivity of Human Malaria Parasites to Antimalarial Drugs","author":"Basco","year":"2007"},{"key":"2024103109155071200_jphp12147-cit-0012","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1128\/AAC.50.3.1045-1053.2006","article-title":"Mefloquine induces dose-related neurological effects in a rat model","volume":"50","author":"Dow","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"2024103109155071200_jphp12147-cit-0013","first-page":"255","article-title":"Effects of mefloquine on Ca2+ uptake by crude microsomes of rabbit skeletal muscle","volume":"329","author":"Go","year":"1995","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"2024103109155071200_jphp12147-cit-0014","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1023\/A:1013098213770","article-title":"The enantioselective binding of mefloquine enantiomers to P-glycoprotein determined using an immobilized P-glycoprotein liquid chromatographic stationary phase","volume":"18","author":"Lu","year":"2001","journal-title":"Pharm Res"},{"key":"2024103109155071200_jphp12147-cit-0015","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0304-4165(00)00160-4","article-title":"Interactions of racemic mefloquine and its enantiomers with P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT","volume":"1524","author":"Pham","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"2024103109155071200_jphp12147-cit-0016","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/sj.bjp.0703638","article-title":"The antimalarial agent mefloquine inhibits ATP-sensitive K-channels","volume":"131","author":"Gribble","year":"2000","journal-title":"Br J Pharmacol"},{"key":"2024103109155071200_jphp12147-cit-0017","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0163-7258(93)90056-J","article-title":"Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum","volume":"57","author":"Slater","year":"1993","journal-title":"Pharmacol Ther"},{"key":"2024103109155071200_jphp12147-cit-0018","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1128\/AAC.13.6.1011","article-title":"Antimalarial activities of various 4-quinolonemethanols with special attention to WR-142,490 (mefloquine)","volume":"13","author":"Schmidt","year":"1978","journal-title":"Antimicrob Agents Chemother"},{"key":"2024103109155071200_jphp12147-cit-0019","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1128\/AAC.21.4.581","article-title":"The antimalarial drug mefloquine binds to membrane phospholipids","volume":"21","author":"Chevli","year":"1982","journal-title":"Antimicrob Agents Chemother"},{"key":"2024103109155071200_jphp12147-cit-0020","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0166-6851(96)02732-6","article-title":"Photoaffinity labeling of mefloquine-binding proteins in human serum, uninfected erythrocytes and Plasmodium falciparum-infected erythrocytes","volume":"82","author":"Desneves","year":"1996","journal-title":"Mol Biochem Parasitol"},{"key":"2024103109155071200_jphp12147-cit-0021","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/0167-4889(84)90007-7","article-title":"On the mechanism for the red-cell accumulation of mefloquine, an antimalarial drug","volume":"803","author":"San George","year":"1984","journal-title":"Biochim Biophys Acta"},{"key":"2024103109155071200_jphp12147-cit-0022","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000238062","article-title":"Single dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites","volume":"28","author":"Schwartz","year":"1982","journal-title":"Chemotherapy"},{"key":"2024103109155071200_jphp12147-cit-0023","first-page":"845","article-title":"Antiprotozoal drugs","volume-title":"Basic & Clinical Pharmacology","author":"Rosenthal","year":"2004"},{"issue":"4","key":"2024103109155071200_jphp12147-cit-0024","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD006491.pub2","article-title":"Drugs for preventing malaria in travellers","author":"Jacquerioz","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"2024103109155071200_jphp12147-cit-0025","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2165\/00002018-200427030-00005","article-title":"The risk of severe depression, psychosis or panic attacks with prophylactic antimalarials","volume":"27","author":"Meier","year":"2004","journal-title":"Drug Saf"},{"key":"2024103109155071200_jphp12147-cit-0026","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1177\/0883073809332700","article-title":"Childhood mefloquine-induced mania and psychosis: a case report","volume":"24","author":"Thapa","year":"2009","journal-title":"J Child Neurol"},{"key":"2024103109155071200_jphp12147-cit-0027","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2875-2-14","article-title":"The acute neurotoxicity of mefloquine may be mediated through a disruption of calcium homeostasis and ER function in vitro","volume":"2","author":"Dow","year":"2003","journal-title":"Malar J"},{"key":"2024103109155071200_jphp12147-cit-0028","first-page":"11","article-title":"Drug delivery \u2013 Where now?","volume-title":"Drug Delivery Systems: Fundamentals and Techniques","author":"Gardner","year":"1987"},{"key":"2024103109155071200_jphp12147-cit-0029","first-page":"15","article-title":"Poorly soluble drugs, a challenge in drug delivery","volume-title":"Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs","author":"Speiser","year":"1998"},{"key":"2024103109155071200_jphp12147-cit-0030","doi-asserted-by":"crossref","first-page":"263","DOI":"10.18433\/J3CS3F","article-title":"Nasal delivery of recombinant human growth hormone: in vivo evaluation with Pheroid technology and N-trimethyl chitosan chloride","volume":"13","author":"Steyn","year":"2010","journal-title":"J Pharm Pharm Sci"},{"key":"2024103109155071200_jphp12147-cit-0031","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijpharm.2009.10.031","article-title":"Enhancement of nasal and intestinal calcitonin delivery by the novel PheroidTM fatty acid based delivery system, and by N-trimethyl chitosan chloride","volume":"385","author":"Du Plessis","year":"2010","journal-title":"Int J Pharm"},{"key":"2024103109155071200_jphp12147-cit-0032","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ijpharm.2011.05.003","article-title":"Absorption of the novel artemisinin derivatives artemisone and artemiside: potential application of Pheroid\u2122 technology","volume":"414","author":"Steyn","year":"2011","journal-title":"Int J Pharm"},{"key":"2024103109155071200_jphp12147-cit-0033","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijpharm.2011.01.050","article-title":"Evaluation of the physical properties and stability of two lipid drug delivery systems containing mefloquine","volume":"409","author":"Slabbert","year":"2011","journal-title":"Int J Pharm"},{"key":"2024103109155071200_jphp12147-cit-0034","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/ja.2012.89","article-title":"In vitro activity of Pheroid vesicles containing antibiotics against Plasmodium falciparum","volume":"65","author":"Du Plessis","year":"2012","journal-title":"J Antibiot (Tokyo)"},{"key":"2024103109155071200_jphp12147-cit-0035","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/IJN.S596","article-title":"Drug delivery and nanoparticles: applications and hazards","volume":"3","author":"De Jong","year":"2008","journal-title":"Int J Nanomedicine"},{"key":"2024103109155071200_jphp12147-cit-0036","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/(SICI)1097-0320(20000201)39:2<166::AID-CYTO10>3.0.CO;2-M","article-title":"Determination of liposome size distribution by flow cytometry","volume":"39","author":"Vorauer-Uhl","year":"2000","journal-title":"Cytometry"},{"key":"2024103109155071200_jphp12147-cit-0037","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0731-7085(01)00635-5","article-title":"A rapid spectrophotometric method for the determination of mefloquine hydrochloride","volume":"27","author":"Rao","year":"2002","journal-title":"J Pharm Biomed Anal"},{"key":"2024103109155071200_jphp12147-cit-0038","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1645\/0022-3395(2005)091[0484:HMPICC]2.0.CO;2","article-title":"Human malaria parasites in continuous culture","volume":"91","author":"Trager","year":"1976","journal-title":"J Parasitol"},{"key":"2024103109155071200_jphp12147-cit-0039","doi-asserted-by":"crossref","first-page":"e1001169","DOI":"10.1371\/journal.pmed.1001169","article-title":"The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites","volume":"9","author":"Delves","year":"2012","journal-title":"PLoS Med"},{"key":"2024103109155071200_jphp12147-cit-0040","first-page":"64","article-title":"Lysis of human red blood cells in the presence of various cosolvents","volume":"39","author":"Reed","year":"1985","journal-title":"J Parenter Sci Technol"},{"key":"2024103109155071200_jphp12147-cit-0041","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/jps.22249","article-title":"Biowaver monographs for immediate release solid oral dosage forms: mefloquine hydrochloride","volume":"100","author":"Strauch","year":"2011","journal-title":"J Pharm Sci"},{"key":"2024103109155071200_jphp12147-cit-0042","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1128\/AAC.01479-06","article-title":"Effects of piperaquine, and amodiaquine on drug uptake and of these in combination with dihydroartemisinin against drug-sensitive and-resistant Plasmodium falciparum strains","volume":"51","author":"Fivelman","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2024103109155071200_jphp12147-cit-0043","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.trstmh.2005.04.016","article-title":"Fatty food does not alter the blood mefloquine concentrations in the treatment of falciparum malaria","volume":"99","author":"Van Hoang Dao","year":"2005","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2024103109155071200_jphp12147-cit-0044","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/jps.20627","article-title":"In vitro hemolysis: guidance for the pharmaceutical scientist","volume":"95","author":"Amin","year":"2006","journal-title":"J Pharm Sci"},{"key":"2024103109155071200_jphp12147-cit-0045","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1021\/js970184o","article-title":"Lysis of human red blood cells. Comparison of in vitro and in vivo hemolysis data","volume":"86","author":"Krzyzaniak","year":"1997","journal-title":"J Pharm Sci"},{"key":"2024103109155071200_jphp12147-cit-0046","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jpba.2005.06.013","article-title":"In vitro studies of the hemolytic activity of microemulsions in human erythrocytes","volume":"39","author":"Aparicio","year":"2005","journal-title":"J Pharm Biomed Anal"},{"key":"2024103109155071200_jphp12147-cit-0047","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/0006-2952(88)90549-7","article-title":"Effects of quinoline-containing antimalarials on the erythrocytes membrane and their significance to drug action on Plasmodium falciparum","volume":"15","author":"Ginsburg","year":"1988","journal-title":"Biochem Pharmacol"},{"key":"2024103109155071200_jphp12147-cit-0048","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.neulet.2012.03.040","article-title":"Suppression of autophagy exacerbates mefloquine-mediated cell death","volume":"515","author":"Shin","year":"2012","journal-title":"Neurosci Lett"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12147","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12147","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/1\/14\/60252149\/jphp12147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/1\/14\/60252149\/jphp12147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T05:21:45Z","timestamp":1730352105000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/66\/1\/14\/6127916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,1]]},"published-print":{"date-parts":[[2014,1,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.12147","relation":{},"ISSN":["2042-7158","0022-3573"],"issn-type":[{"value":"2042-7158","type":"electronic"},{"value":"0022-3573","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,1]]},"published":{"date-parts":[[2014,1,1]]}}}