Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ¹H molecular diffusion NMR and ¹⁹F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ¹H molecular diffusion nuclear magnetic resonance (NMR) and ¹⁹F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ¹⁹F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Model of Drug-Loaded Fluorocarbon-Based Micelles Studied by Electron-Spin Induced ^(19)F Relaxation NMR and Molecular Dynamics Simulation

R_f-IPDU-PEGs belong to a class of fluoroalkyl-ended poly(ethylene glycol) polymers (R_f-PEGs), where the IPDU (isophorone diurethane) functions as a linker to connect each end of the PEG chain to a fluoroalkyl group. The R_f-IPDU-PEGs form hydrogels in water with favorable sol−gel coexistence properties. Thus, they are promising for use as drug delivery agents. In this study, we introduce an electron-spin induced ^(19)F relaxation NMR technique to probe the location and drug-loading capacity for an electron-spin labeled hydrophobic drug, CT (chlorambucil-tempol adduct), enclosed in the R_f-IPDU-PEG micelle. With the assistance of molecular dynamics simulations, a clear idea regarding the structures of the R_f-IPDU-PEG micelle and its CT-loaded micelle was revealed. The significance of this research lies in the finding that the hydrophobic drug molecules were loaded within the intermediate IPDU shells of the R_f-IPDU-PEG micelles. The molecular structures of IPDU and that of CT are favorably comparable. Consequently, it appears that this study opens a window to modify the linker between the R_f group and the PEG chain for achieving customized structure-based drug-loading capabilities for these hydrogels, while the advantage of the strong affinity among the R_f groups to hold individual micelles together and to interconnect the micellar network is still retained in hopes of maintaining the sol−gel coexistence of the R_f-PEGs

Sequential Photooxidation of a Pt(II) (Diimine)cysteamine Complex: Intermolecular Oxygen Atom Transfer versus Sulfinate Formation

The thiolato complex [platinum­(II) (bipyridine)­(<i>N</i>,<i>S</i>-aminoethanethiolate)]⁺Ch^– (<b>1</b>) undergoes sequential reactions with singlet oxygen to initially form the corresponding sulfenato complex [platinum­(II) (bipyridine)­(<i>N</i>,<i>S</i>(O)-aminoethansulfenate)]⁺ (<b>2</b>) followed by a much slower reaction to the corresponding sulfinato complex. In contrast with many platinum dithiolato complexes, <b>1</b> does not produce any singlet oxygen, but its rate constant for singlet oxygen removal (<i>k</i>_T) is quite large (3.2 × 10⁷ M^–1 s^–1) and chemical reaction accounts for ca. 25% of the value of <i>k</i>_T. The behavior of <b>1</b> is strikingly different from that of the complex platinum­(II) (bipyridine)­(1,2-benzenditholate) (<b>4</b>). The latter complex reacts with ¹O₂ (either from an external sensitizer or via a self-sensitized pathway) to form a sulfinato complex. These two very different reactivity pathways imply different mechanistic pathways: The reaction of <b>1</b> with ¹O₂ must involve O–O bond cleavage and intermolecular oxygen atom transfer, while the reactive intermediate in complex <b>4</b> collapses intramolecularly to the sulfinato moiety