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Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems.

ABSTRACT: Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.

SUBMITTER: Vanslambrouck S

PROVIDER: S-EPMC8003835 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Superhydrophobic Melamine Sponge Coated with Striped Polydimethylsiloxane by Thiol-Ene Click Reaction for Efficient Oil/Water Separation.

Project description:Superhydrophobic and oleophilic sponges have been demonstrated as promising candidates for oil/water separation. However, there are still challenges in large-scale fabrication of superhydrophobic sponges with low cost and feasible method for industrial applications. Herein, we report a superhydrophobic and oleophilic melamine sponge functionalized by a uniform polydimethylsiloxane (PDMS) film that can be easily coated onto the sponge skeleton through UV-assisted thiol-ene click reactions. The PDMS films are characterized by a hierarchically striped microstructure with an average distance less than 2 μm. Because of the striped microstructure and the hydrophobic property of silicone, a high contact angle of 156.2° was achieved. Importantly, the interconnected open-cell structure of the melamine sponge was preserved by adapting the thickness of the PDMS film. The PDMS-coated melamine sponge exhibited a desirable absorption capacity of 103-179 times its own weight with oils and organic solvents. The excellent mechanical properties of melamine and the flexibility of PDMS enable the PDMS-coated melamine sponges to be squeezed repeatedly without collapsing. This study offers a robust and effective approach in large-scale preparation of a superhydrophobic sponge for large-scale oil spill containment and environmental remediation by the inexpensive commercial polymethylvinylsilicone and facile dip-coating/UV-curing method.

| S-EPMC6641746 | biostudies-literature

Rapid assembly of a library of lipophilic iminosugars via the thiol-ene reaction yields promising pharmacological chaperones for the treatment of Gaucher disease.

Project description:A highly divergent route to lipophilic iminosugars that utilizes the thiol-ene reaction was developed to enable the rapid synthesis of a collection of 16 dideoxyiminoxylitols bearing various different lipophilic substituents. Enzyme kinetic analyses revealed that a number of these products are potent, low-nanomolar inhibitors of human glucocerebrosidase that stabilize the enzyme to thermal denaturation by up to 20 K. Cell based assays conducted on Gaucher disease patient derived fibroblasts demonstrated that administration of the compounds can increase lysosomal glucocerebrosidase activity levels by therapeutically relevant amounts, as much as 3.2-fold in cells homozygous for the p.N370S mutation and 1.4-fold in cells homozygous for the p.L444P mutation. Several compounds elicited this increase in enzyme activity over a relatively wide dosage range. The data assembled here illustrate how the lipophilic moiety common to many glucocerebrosidase inhibitors might be used to optimize a lead compound's ability to chaperone the protein in cellulo. The flexibility of this synthetic strategy makes it an attractive approach to the rapid optimization of glycosidase inhibitor potency and pharmacokinetic behavior.

| S-EPMC3380069 | biostudies-literature

Cell-mediated delivery of glucocorticoids from thiol-ene hydrogels.

Project description:Thiol-ene-based poly(ethylene glycol) (PEG) hydrogels provide a unique functional platform for the sustained and localized delivery of bioactive small molecules like glucocorticoids. As a proof of concept, the synthetic glucocorticoid Dexamethasone (Dex) was conjugated to the N-terminus of a matrix metalloproteinase(MMP)-degradable peptide, which was then easily co-polymerized into PEG gel scaffolds by a thiol-ene polymerization mechanism. The conjugated Dex was locally sequestered until released by cleavage of the MMP-degradable peptide tether triggered by cell-secreted MMPs, and was only available for uptake by local co-encapsulated cells. Elevated alkaline phosphatase (ALP) activities and calcium deposition levels were observed for human mesenchymal stem cells (hMSCs) that were encapsulated in PEG hydrogels functionalized with 10 ?M of a Dexamethasone-conjugated peptide (Dex-peptide). The cellular responses stimulated by the tethered Dex lasted for over 21 days. Using co-culture experiments, hMSCs encapsulated in hydrogels with the MMP-degradable Dex-peptides had elevated levels of ALP activity and calcium deposition, whereas no elevated cellular responses were observed in co-cultured hMSCs surrounding the gel. Moreover, modifying the peptide sequence to alter its susceptibility to cleavage and/or changing the Dex-peptide loading further regulated the hMSC response to Dex at different levels and on different time scales. Collectively, these results demonstrate a tunable system for the delivery of glucocorticoids in a localized and cell-dictated manner.

| S-EPMC3487401 | biostudies-literature

Intermolecular Photocatalytic Chemo-, Stereo- and Regioselective Thiol-Yne-Ene Coupling Reaction.

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| S-EPMC9313788 | biostudies-literature

Thiol-Ene Click Reaction Initiated Rapid Gelation of PEGDA/Silk Fibroin Hydrogels.

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| S-EPMC6960922 | biostudies-literature

Synthesis of non-linear protein dimers through a genetically encoded Thiol-ene reaction.

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| S-EPMC4152134 | biostudies-literature

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| S-EPMC5779077 | biostudies-literature

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Project description:The carbonyl ene reaction of 2-methylenetetrahydropyrans provides a rapid, high yielding route for the preparation of ?-hydroxydihydropyrans under mild conditions. This process provides a new entry for the synthesis of 2-substituted tetrahydropyrans and for the direct introduction of oxygen heterocycles into molecular frameworks.

| S-EPMC3946575 | biostudies-literature

Preparation and Preliminary Dielectric Characterization of Structured C60-Thiol-Ene Polymer Nanocomposites Assembled Using the Thiol-Ene Click Reaction.

Project description:Fullerene-containing materials have the ability to store and release electrical energy. Therefore, fullerenes may ultimately find use in high-voltage equipment devices or as super capacitors for high electric energy storage due to this ease of manipulating their excellent dielectric properties and their high volume resistivity. A series of structured fullerene (C60) polymer nanocomposites were assembled using the thiol-ene click reaction, between alkyl thiols and allyl functionalized C60 derivatives. The resulting high-density C60-urethane-thiol-ene (C60-Thiol-Ene) networks possessed excellent mechanical properties. These novel networks were characterized using standard techniques, including infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermal gravimetric analysis (TGA). The dielectric spectra for the prepared samples were determined over a broad frequency range at room temperature using a broadband dielectric spectrometer and a semiconductor characterization system. The changes in thermo-mechanical and electrical properties of these novel fullerene-thiol-ene composite films were measured as a function of the C60 content, and samples characterized by high dielectric permittivity and low dielectric loss were produced. In this process, variations in chemical composition of the networks were correlated to performance characteristics.

| S-EPMC5458907 | biostudies-other

Poly(ethylene glycol) hydrogels formed by thiol-ene photopolymerization for enzyme-responsive protein delivery.

Project description:Degradable hydrogels have been extensively used in biomedical applications such as drug delivery, and recent interest has grown in hydrogels that degrade in recognition of a cellular response. This contribution describes a poly(ethylene glycol) (PEG) hydrogel platform with human neutrophil elastase (HNE) sensitive peptide cross-links formed using thiol-ene photopolymerization rendering the gel degradable at sites of inflammation. Further, protein therapeutics can be physically entrapped within the network and selectively released upon exposure to HNE. HNE-responsive hydrogels exhibited surface erosion where the degradation kinetics was influenced by changes in peptide k(cat), concentration of HNE, and concentration of peptide within the gel. Using this platform, we were able to achieve controlled, zero-order release of bovine serum albumin (BSA) in the presence of HNE, and release was arrested in the absence of HNE. To further exploit the advantages of surface eroding delivery systems, a smaller protein (carbonic anhydrase) was delivered at the same rate as BSA and only dependent on gel formulation and environmental conditions. Also, protein release was predicted from a 3-layered hydrogel device using mass loss data. Lastly, the bioactivity of lysozyme was maintained above 90% following the exposure to thiol-ene photopolymerization conditions.

| S-EPMC2761537 | biostudies-literature

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