Conjugation of High-Molecular Weight Poly(ethylene glycol) to Cytokines: Granulocyte-Macrophage Colony-Stimulating Factors as Model Substrates

Sherman, Merry R.; Williams, L. David; Saifer, Mark G.P.; French, John A.; Kwak, Larry W.; Oppenheim, Joost J.

doi:10.1021/bk-1997-0680.ch011

Cited by 28 publications

(17 citation statements)

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“…However, studies of PEG in solution showed that each ethylene glycol sub-unit is tightly associated with two or three water molecules. The binding of water to PEG makes PEGylated compounds function as though they are three to nine times larger than a corresponding soluble protein of similar molecular weight (32,33). Clinically used PEG polymers with associated water molecules act like a shield to protect the attached drug from enzymatic degradation, inhibit interactions with cell surface proteins and provide increased size to prevent rapid renal filtration and clearance.…”

Section: Discussionmentioning

confidence: 99%

Peritoneal Macrophage Uptake, Pharmacokinetics and Biodistribution of Macrophage-Targeted PEG-fMLF (N-Formyl-Methionyl-Leucyl-Phenylalanine) Nanocarriers for Improving HIV Drug Delivery

Wan

Pooyan

et al. 2007

Pharm Res

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Purpose-To assess in vivo macrophage targeting potential of PEG-fMLF nanocarriers and to investigate their biodistribution, peritoneal macrophage uptake, and pharmacokinetics.Methods-Multiple copies of fMLF were conjugated to purchased and novel (branched, peptidebased) PEG nanocarriers. Peritoneal macrophage uptake was evaluated in mice 4 hours after IP administration of fluorescence-labeled PEG-fMLF nanocarriers. Pharmacokinetics and biodistribution were determined in rats after IV administration of tritiated PEG-fMLF nanocarriers.Results-Attachment of one, two, or four fMLF copies increased uptake in macrophages by 3.8-, 11.3-, and 23.6-fold compared to PEG without fMLF. Pharmacokinetic properties and tissue distribution also differed between nanocarriers with and without fMLF. Attachment of fMLF residues increased the t 1/2 of PEG 5K by threefold but decreased the t 1/2 of PEG 20K by 40%. Attachment of fMLF increased accumulation of nanocarriers into macrophages of liver, kidneys and spleen. However, on a molar basis, penetration was equivalent suggesting nanocarrier size and targeting moieties are important determinants.Conclusions-These results demonstrate the feasibility for targeting macrophages, a primary HIV reservoir site. However, these studies also suggest that balancing peripheral tissue penetration (a size-dependent phenomenon) versus target cell uptake specificity remains a challenge to overcome.

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Section: Discussionmentioning

confidence: 99%

Peritoneal Macrophage Uptake, Pharmacokinetics and Biodistribution of Macrophage-Targeted PEG-fMLF (N-Formyl-Methionyl-Leucyl-Phenylalanine) Nanocarriers for Improving HIV Drug Delivery

Wan

Pooyan

et al. 2007

Pharm Res

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“…In medical and pharmaceutical applications, PEG hydrogels absorb water and prolong the time of drug release and metabolism, thereby resulting in a decreased frequency of drug injections 23,24) . In dentistry, the PEG hydrogel technology could be leveraged and applied to help reduce dentin permeability by decreasing fluid movement through the dentinal tubules and protecting against water contamination on the dentin substrate.…”

Section: Discussionmentioning

confidence: 99%

Measurement of shear bond strength to intact dentin

et al. 2010

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Previously, we reported that the integrity of a resin composite restoration deteriorated when the dentin cavity wall was decalcified by conditioning. In this study, to evaluate the bonding between dentin adhesive and non-decalcified dentin surface, we experimented with a novel method of using a high-pressure water spray device to prepare smear layer-free dentin surfaces. When the smear layer was removed, shear bond strength significantly increased regardless of the removal method employed. Further, with glyceryl monomethacrylate (GM) priming, no significant differences in bond strength were observed among these smear layer removal methods: ethylenediamine tetraacetic acid (EDTA) conditioning, phosphoric acid conditioning, and removal by water spray. It was also found that GM priming was key to achieving marginal integrity, whereas contraction gap width increased with phosphoric acid conditioning. It was thus concluded that the efficacy of a dentin adhesive should be evaluated by consistently observing the contraction gap in three-dimensional cavities rather than by mere measurement of bond strength to a flat dentin surface.

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“…Polyethylene glycol (PEG) is used medically for injectable drugs 15,16) . Since PEGs absorb water and form a hydrogel capsule, the time required for drug release and metabolism is prolonged.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that drug release is delayed when the drug is callused with polyethylene glycol (PEG) because of the water absorption properties of PEG 15,16) . Consequently, it is possible to reduce the frequency of injections by drug pegylation.…”

Section: Introductionmentioning

confidence: 99%

Priming Effects of Triethylene Glycol and Triethylene Glycol Monomethacrylate on Dentin Bonding

Kusunoki¹,

Itoh²,

Utsumi³

et al. 2007

Dent. Mater. J.

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The objective of this study was to evaluate the effects of triethylene glycol (TEG) and triethylene glycol monomethacrylate (TEGMA) solutions as dentin primers on dentin bonding. To this end, wall-to-wall polymerization contraction gap width of a resin composite in a cylindrical dentin cavity and shear bond strength to a flat dentin surface were measured. Dentin was pretreated with an experimental dentin bonding system -consisting of 0.5 M ethylenediaminetetraacetic acid conditioner, TEG or TEGMA primer, and Clearfil Photo Bond bonding agent -prior to resin composite filling. When the cavity was primed with an aqueous solution of 35 vol％ TEG, 35 or 45 vol％ TEGMA for a few seconds, contraction gap formation was prevented completely. Then, among these three gap-free groups, there were no significant differences in shear bond strength. It was thus shown that both TEG and TEGMA were highly effective dentin primers, completely preventing contraction gap formation even when they were applied for only a few seconds.

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Conjugation of High-Molecular Weight Poly(ethylene glycol) to Cytokines: Granulocyte-Macrophage Colony-Stimulating Factors as Model Substrates

Cited by 28 publications

References 0 publications

Peritoneal Macrophage Uptake, Pharmacokinetics and Biodistribution of Macrophage-Targeted PEG-fMLF (N-Formyl-Methionyl-Leucyl-Phenylalanine) Nanocarriers for Improving HIV Drug Delivery

Peritoneal Macrophage Uptake, Pharmacokinetics and Biodistribution of Macrophage-Targeted PEG-fMLF (N-Formyl-Methionyl-Leucyl-Phenylalanine) Nanocarriers for Improving HIV Drug Delivery

Measurement of shear bond strength to intact dentin

Priming Effects of Triethylene Glycol and Triethylene Glycol Monomethacrylate on Dentin Bonding

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