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The Influence of Stabilizer and Bioadhesive Polymer on the Permeation-Enhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker
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  • The Influence of Stabilizer and Bioadhesive Polymer on the Permeation-Enhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker
  • The Influence of Stabilizer and Bioadhesive Polymer on the Permeation-Enhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker
저자명
Song. Keon-Hyoung,Eddington. Natalie D.
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2012년|35권 2호|pp.359-366 (8 pages)
발행정보
대한약학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential. Thus, this paper focused on the susceptibility of AT1002 for identifying additives to minimize the instability of AT1002, and the permeation-enhancing effect of AT1002 when co-administered with a bioadhesive polymer. The stability study showed that AT1002 were unstable in neutral to basic pH conditions and with increasing incubation time, and 5% dextrose and the 1% mixture of amino acids (arginine, cysteine, glycine) significantly minimized the instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the intranasal study of a paracellular marker, the administration of mannitol with AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17-fold increases in $C_{max}$ and $AUC_{0-360min}$ in the presence of carrageenan over the control. Thus, the addition of carrageenan as a bioadhesive polymer and dextrose as a stabilizer together with AT1002 may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents.