title: Multi-laminated metal hydroxide nanocontainers for oral-specific delivery for bioavailability improvement and treatment of inflammatory paw edema in mice.
abstract: Multiple layers of pH-sensitive enteric copolymers were coated over layered double hydroxide (LDH) nanoparticles for controllable drug release and improved solubility of hydrophobic drugs. The nano-sized LDH carriers significantly improved the accessibility of sulfasalazine molecules that have positively charged frameworks. In addition, the successful encapsulation of negatively charged enteric copolymers was achieved via electrostatic attractions. The multi-layered enteric polymer coating could potentially protect nanoparticle dissolution at gastric pH and accelerate the dissolution velocity, which would improve the drug bioavailability in the colon. Next, biological studies of this formulation indicated a highly protective effect from the scavenging of superoxide free radicals and diethyl maleate (DEM) induced lipid peroxidation, which are major cell signalling pathways for inflammation. The histological view of the liver and kidney sections revealed that the nanoformulation is safe and highly biocompatible. The animal studies conducted via paw inflammation induced by complete Freund's adjuvant (CFA) revealed that enteric-coated LDH-sulfasalazine nanoparticles provided a sustained release that maintained the sulfasalazine concentrations in a therapeutic window. Therefore, this nanoformulation exhibited preferential efficacy in reducing the CFA-induced inflammation especially at day 4.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Ranjith Kumar
authors.initials: RK
authors.lastname: Kankala
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Yaswanth
authors.initials: Y
authors.lastname: Kuthati
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Huei-Wun
authors.initials: HW
authors.lastname: Sie
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Shih
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan; Department of Physiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Sheng-I
authors.initials: SI
authors.lastname: Lue
authors.affiliation: Department of Chemistry, Kakatiya University, Warangal, India.
authors.forename: Shravankumar
authors.initials: S
authors.lastname: Kankala
authors.affiliation: Department of Physics, National Chung-Hsing University, Taichung 402, Taiwan.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Jeng
authors.affiliation: Department of Chemistry, Tamkang University, New Taipei City 251, Taiwan.
authors.forename: Jin-Pei
authors.initials: JP
authors.lastname: Deng
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan. Electronic address: cliu@mail.ndhu.edu.tw.
authors.forename: Chen-Lun
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan. Electronic address: chlee016@mail.ndhu.edu.tw.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004487:Edema / Q000188:drug therapy*; D019073:HT29 Cells; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D012460:Sulfasalazine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D006878:Hydroxides; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D012460:Sulfasalazine; C031356:hydroxide ion
keywords: Eudragit copolymer; Inflammatory; Layered double hydroxides; Nanoparticles; Oral drug delivery; Sulfasalazine