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제122회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Artesunate-Zinc Basic Salt Nanohybrid as a Novel Antimalarial Drug; Oral and Intravenous Administrations

2018년 8월 31일 16시 00분 40초
MAT.O-16 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 10시 : 45분
Material Chemisty - Oral Presentation of Young Material Chemists
저자 및
Jiyeong Kim, Goeun Choi1, Jin-ho Choy1,*
Chemistry Department of NanoScience, Ewha Womans University, Korea
1Department of Chemistry and NanoScience, Ewha Womans University, Korea
Artesunate (AS) is known as a water soluble anti-malarial drug (52.2 mg/L), but its bioavailability is rather low due to its limitted aqueous solubility. In order to overcome this problem, a novel drug delivery system with hydrophilic function was suggested and demonstrated by intercalating AS into inorganic nano-vehicle like zinc basic salt (ZBS) via co-precipitation method. According to the powder x-ray diffraction analysis, the basal spacing of AS-ZBS nanohybrid was determined to be 2.88nm, indicating that AS molecules were successfully incorporated into the interlayer space of 2D ZBS host lattice. And the intracrystalline structure and molecular orientation of AS in the lattice could be confirmed by comparing the experimental 1-D electron density mapping result from the (00l) XRD data with the calculated one from the structure model of AS-ZBS, and partly by TEM analysis as well. The FT-infrared spectra revealed that AS molecules were deprotonated and electrostatically incorporated between cationic zinc hydroxide layers without any structural modifications. According to the CHNS, TG and HPLC analyses, the AS content in AS-ZBS was determined to be 45.8 wt%. In order to hold down dissolution and burst release of AS from AS-ZBS in a gastric juice condition, the AS-ZBS was further coated with an enteric coating polymer like Eudragit® L100 (AS-ZBS-L100), which dissolves in the basic environment of the intestines, for controlling the rate of drug release with respect to the pH values in the digestive tract. As expected, the AS-ZBS-L100 nanohybrid showed a remarkable increase in the release rate of AS in a simulated intestinal condition (pH 6.8) compared to the intact AS. In addition, we have performed in-vivo pharmacokinetic study in rats via oral administration in order to compare the absorption of AS out of the AS-ZBS-L100 nanohybrid with that of intact AS. Surprisingly, it was found that the former was ~6 times larger than the latter due to an enhanced solubility of AS thanks to the hybridization with hydrophilic ZBS. Therefore, AS-ZBS-L100 could be suggested as a promising drug delivery system for improving drug solubility and absorption. Additionally, an attempt was made to encapsulate AS molecules into layered double hydroxide (LDH) for intravenous injection. All the in-vitro results including drug release behavior in the simulated body fluid will be demonstrated in-detail in this presentation.