title: 2D Inorganic-Antimalarial Drug-Polymer Hybrid with pH-Responsive Solubility.
abstract: Artesunic acid (ASH), an antimalarial drug, has low oral bioavailability due to its low aqueous solubility. To overcome this problem, artesunate (AS) was intercalated into zinc basic salt (ZBS) via co-precipitation. AS was immobilized with a tilted double layer arrangement, which was also confirmed by XRD and 1-D electron density mapping. In order to decrease the release rate of AS under gastrointestinal conditions and to simultaneously increase the release rate of AS under intestinal conditions, ZBS-AS was coated with EUDRAGIT L100 (ZBS-AS-L100). Finally, we performed an in-vivo pharmacokinetic study to compare the oral bioavailability of AS of ZBS-AS-L100 with that of ASH. Surprisingly, it was found that the former is 5.5 times greater than the latter due to an enhanced solubility of AS thanks to the ternary hybridization with ZBS and EUDRAGIT L100. Therefore, the present ZBS-AS-L100 system has a great potential as a novel antimalarial drug formulation with pH selectivity and enhanced bioavailability.
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Ji-Yeong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Goeun
authors.initials: G
authors.lastname: Choi
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Dae-Hwan
authors.initials: DH
authors.lastname: Park
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, Seoul, 139-774, South Korea.
authors.forename: Mi-Rea
authors.initials: MR
authors.lastname: Jo
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, Seoul, 139-774, South Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, South Korea. jhchoy@ewha.ac.kr.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choy
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D011232:Chemical Precipitation; D006863:Hydrogen-Ion Concentration; D008297:Male; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013386:Succinates / Q000737:chemistry* / Q000493:pharmacokinetics*; D017967:Zinc Compounds
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011108:Polymers; D011109:Polymethacrylic Acids; D013386:Succinates; D017967:Zinc Compounds; C038300:methylmethacrylate-methacrylic acid copolymer; C111789:artesunic acid
keywords: artesunic acid; bioavailability; layered compounds; polymers; zinc basic salt