title: Assessment of the safety, targeting, and distribution characteristics of a novel pH-sensitive hydrogel.
abstract: In our previous study, we synthesized a pH-sensitive hydrogel based on poly (ɛ-caprolactone) (PCL), Pluronic (Poloxamer) and methacrylic acid (MAA) using UV-initiated free-radical polymerization. In the present study, we evaluated the safety of the obtained GMA-PCFC-GMA copolymer and a P(CFC-MAA-MEG) hydrogel both in vitro and in vivo. The pharmacokinetics study and distribution characteristics of dexamethasone in rat blood and mouse colon were investigated in detail. The in vitro toxicity of the GMA-PCFC-GMA copolymer was evaluated using a cell viability assay with HEK293 cells. An acute oral toxicity test was conducted by orally administering mice with a total of 10,000 mg/kg body weight of the P(CFC-MAA-MEG) hydrogel. The mice were then observed continuously for 14 days. After which, they were sacrificed and their blood collected for routine blood and serum chemistry tests. Pharmacokinetic and colonic tissue distribution studies were conducted using high-performance liquid chromatography to detect the concentration of dexamethasone in rat blood and mouse colon tissue. All of the results indicated that both the GMA-PCFC-GMA copolymer and P(CFC-MAA-MEG) hydrogel were nontoxic. Moreover, the hydrogel significantly enhanced the colon-targeting behavior of dexamethasone. These results suggested that the novel hydrogel has great potential in colon-targeted drug delivery.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Cuiyu
authors.initials: C
authors.lastname: You
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: perpetual1003@mail.xjtu.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: xajdxjf@mail.xjtu.edu.cn.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: Acute toxicity; Cytotoxicity; Pharmacokinetics study; pH-sensitive hydrogel