title: Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray.
abstract: In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 μg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China.
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Omari-Siaw
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China. Electronic address: zhuyuanemail@126.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, P.R. China. Electronic address: xmxu@ujs.edu.cn.
authors.forename: Ximing
authors.initials: X
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D012765:Shikimic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D012765:Shikimic Acid; C033616:poly(lactide)
keywords: PLA; absorption; burst release; pharmacokinetics; submicron particles