title: Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles.
abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Moonjeong
authors.initials: M
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Woo Seong
authors.initials: WS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Bok Luel
authors.initials: BL
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
mesh_terms: D000818:Animals; D019819:Budesonide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D051381:Rats
chemical_list: D019819:Budesonide
keywords: azo-polyurethane; budesonide; colitis; colon-targeted nanoparticles; methacrylate copolymer