title: Thiomer nanoparticles: stabilization via covalent cross-linking.
abstract: The purpose of this study was the development of stable thiomer nanoparticles for mucosal drug delivery. Chitosan-thioglycolic acid (chitosan-TGA) nanoparticles (NP) were formed via ionic gelation with tripolyphosphate (TPP). In order to stabilize the NP inter- and intra-molecular disulfide bonds were formed via controlled oxidation with hydrogen peroxide (H₂O₂). Thereafter, stability was investigated in saline and simulated body fluids at pH 2 and pH 5.5 via optical density measurements. The mucoadhesive properties were evaluated in vitro on freshly excised porcine intestinal mucosa via the rotating cylinder method. Particles had a mean size of 158 ± 8 nm and a zeta potential of ~ + 16 mV. Three different degrees of oxidation were adjusted by the addition of H₂O₂ in final concentrations of 10.60 µmol (chitosan-TGA (ox1)), 21.21 µmol (chitosan-TGA (ox2)), and 31.81 µmol (chitosan-TGA (ox3)) leading to 60%, 75%, and 83% of oxidized thiol groups, respectively. More than 99% of chitosan-TGA (ox3) NP, 70% of chitosan-TGA (ox2) NP, and 50% of chitosan-TGA (ox1) NP were stable over a 60-min period in simulated gastric fluid. In contrast, only 10% of unmodified chitosan and chitosan-TGA NP which were just ionically cross-linked remained stable in the same experiment. The adhesion times of covalently cross-linked chitosan-TGA (ox1), chitosan-TGA (ox2), and chitosan-TGA (ox3) were ~ 41-fold, 31-fold, and 25-fold longer in comparison to unmodified ionically cross-linked chitosan. The method described here might be useful for the preparation of stable nanoparticulate drug delivery systems.
authors: Pharmaceutical Technology, University of Innsbruck, Innrain 52, Josef-Möller-Haus, Innsbruck, 6020 Austria.
authors: Jan
authors: J
authors: Barthelmes
authors: Sarah
authors: S
authors: Dünnhaupt
authors: Juliane
authors: J
authors: Hombach
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D000327:Adsorption; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry; D055672:Static Electricity; D013438:Sulfhydryl Compounds / Q000737:chemistry; D034421:Sus scrofa; D013864:Thioglycolates / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D004220:Disulfides; D011122:Polyphosphates; D013438:Sulfhydryl Compounds; D013864:Thioglycolates; C017487:2-mercaptoacetate; D048271:Chitosan; D006861:Hydrogen Peroxide; C005692:triphosphoric acid