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

Mathias EV, Aponte J, Kornfield JA, Ba Y - Colloid Polym Sci (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

ABSTRACT
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, (1)H 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.

No MeSH data available.


Related in: MedlinePlus

Experimental NMR signal attenuations with diffusion time (∆−δ/3) for DMFU in 6KC6 (squares), FU in 6KC6 (diamonds), FU in 6K PEG (upright triangle), and FU in D2O (inverted triangles). The corresponding lines show the data fitting with the first-order exponential decays as shown in Eq. 2
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Fig2: Experimental NMR signal attenuations with diffusion time (∆−δ/3) for DMFU in 6KC6 (squares), FU in 6KC6 (diamonds), FU in 6K PEG (upright triangle), and FU in D2O (inverted triangles). The corresponding lines show the data fitting with the first-order exponential decays as shown in Eq. 2

Mentions: To gather more experimental data in order to find the boundary effect and the exchange effect between the probe molecules in the Rf core/IPDU intermediate-layer region and in the PEG–water phase, PFGSTE diffusion experiments where Δ was varied from 0 to 200 ms while the gradient was fixed at g = 75 G/cm and δ = 1 ms were carried out. The results are shown in Fig. 2, where (∆−δ/3) is used as the unit of the horizontal axis. Besides the samples of FU in 6KC6 hydrogel and DMFU in 6KC6 hydrogel, experiments for FU in 6K PEG solution and FU in D2O were also carried out for the purpose of comparison. All these sets of experimental data fit the following exponential decays well:Fig. 2


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

Mathias EV, Aponte J, Kornfield JA, Ba Y - Colloid Polym Sci (2010)

Experimental NMR signal attenuations with diffusion time (∆−δ/3) for DMFU in 6KC6 (squares), FU in 6KC6 (diamonds), FU in 6K PEG (upright triangle), and FU in D2O (inverted triangles). The corresponding lines show the data fitting with the first-order exponential decays as shown in Eq. 2
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2982959&req=5

Fig2: Experimental NMR signal attenuations with diffusion time (∆−δ/3) for DMFU in 6KC6 (squares), FU in 6KC6 (diamonds), FU in 6K PEG (upright triangle), and FU in D2O (inverted triangles). The corresponding lines show the data fitting with the first-order exponential decays as shown in Eq. 2
Mentions: To gather more experimental data in order to find the boundary effect and the exchange effect between the probe molecules in the Rf core/IPDU intermediate-layer region and in the PEG–water phase, PFGSTE diffusion experiments where Δ was varied from 0 to 200 ms while the gradient was fixed at g = 75 G/cm and δ = 1 ms were carried out. The results are shown in Fig. 2, where (∆−δ/3) is used as the unit of the horizontal axis. Besides the samples of FU in 6KC6 hydrogel and DMFU in 6KC6 hydrogel, experiments for FU in 6K PEG solution and FU in D2O were also carried out for the purpose of comparison. All these sets of experimental data fit the following exponential decays well:Fig. 2

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

ABSTRACT
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, (1)H 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.

No MeSH data available.


Related in: MedlinePlus