| 1. |
- Ahrenstedt, Lage, et al.
(author)
-
Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions
- 2024
-
In: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 95
-
Journal article (peer-reviewed)abstract
- Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Ghirardello, Mattia, et al.
(author)
-
Thiol-Ene and Thiol-Yne-Based Synthesis of Glycodendrimers as Nanomolar Inhibitors of Wheat Germ Agglutinin
- 2014
-
In: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 52:17, s. 2422-2433
-
Journal article (peer-reviewed)abstract
- Alkene and alkyne functional polyester-based dendrimers of generation 1 to 4 have been prepared and reacted under free-radical conditions with 2-acetamido-2-deoxy-1-thio--D-glucose (GlcNAc-SH). As the alkene-dendrimers underwent the addition of one thiyl radical per ene group whereas each yne group of alkyne-dendrimers was saturated by two thiyl radicals, a collection of glycodendrimers with glycan density ranging from six to ninety-six GlcNAc per dendrimer was obtained. The recognition properties of the prepared glycodendrimers toward the wheat germ agglutinin (WGA) were evaluated by enzyme-linked lectin assay (ELLA). The eight glycodendrimers were excellent ligands showing IC50 values in the nanomolar range and relative potencies per sugar unit up to 2.27 e(6) when compared to monosaccharidic GlcNAc used as monovalent reference.
|
|
| 6. |
|
|
| 7. |
- Hed, Yvonne
(author)
-
Multifunctional Dendritic Scaffolds: Synthesis, Characterization and Potential applications
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- The development of materials for advanced applications requires innovative macromolecules with well-defined structures and the inherent ability to be tailored in a straightforward manner. Dendrimers, being a subgroup of the dendritic polymer family, possess properties which fulfill such demands. They have a highly branched architecture with a high number of functional groups and are one of the most well-defined types of macromolecules ever synthesized. However, despite their well-defined nature and high functional density, traditional dendrimers commonly lack diverse chemical functionalities. Therefore, this thesis focuses on the synthesis of more complex dendritic materials to extend their tailoring capacity by introduction of dualfunctionalities for multipurpose actions. It covers the synthesis of dualfunctional dendrimers, dendritic modification of linear poly(ethylene glycol) polymers and cellulose surfaces, and the synthesis of linear dendritic hybrids. The building blocks enabling this synthesis, AB2C monomers, were also developed during this work. The orthogonal nature between click groups (azide, alkyne and alkene) and hydroxyl groups have efficiently been utilized for postfunctionalization by robust click chemistry and traditional esterification reactions. Furthermore, linear dendritic hybrids were synthesized, merging the properties of linear and dendritic macromolecules. The dendritic frameworks were tailored towards the production of bone fracture adhesives, novel biofunctional dendritic hydrogels, biosensors and micellar drug delivery vehicles.
|
|
| 8. |
- Hed, Yvonne, et al.
(author)
-
Multipurpose heterofunctional dendritic scaffolds as crosslinkers towards functional soft hydrogels and implant adhesives in bone fracture applications
- 2013
-
In: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-7518 .- 2050-750X. ; 1:44, s. 6015-6019
-
Journal article (peer-reviewed)abstract
- Two sets of heterofunctional dendritic frameworks displaying an inversed and exact number of ene and azide groups have successfully been synthesized and post-functionalized with biorelevant molecules. Their facile scaffolding ability enabled the fabrication of soft and azide functional dendritic hydrogels with modulus close to muscle tissue. The dendritic scaffolds are furthermore shown to be promising primers for the development of novel bone fracture stabilization adhesives with shear strengths succeeding commercial Histroacryl (R).
|
|
| 9. |
- Hed, Yvonne, et al.
(author)
-
Side-by-side comparison of dendritic-linear hybrids and their hyperbranched analogs as micellar carriers of chemotherapeutics
- 2013
-
In: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 51:19, s. 3992-3996
-
Journal article (peer-reviewed)abstract
- Amphiphilic block copolymers are successfully synthesized possessing a hydrophobic dendritic component based on the bis-MPA monomer and a hydrophilic linear polyethylene glycol (PEG) component. The hybrids were either conjured in small scale using robust click reactions between perfect dendrons and linear PEG or multigram polycondensation of hyperbranched blocks from PEG. In all cases, the amphiphiles were assembled to micelles, were found nontoxic and successfully loaded with the chemotherapeutic doxorubicin.
|
|
| 10. |
- Lo Conte, Mauro, et al.
(author)
-
Exhaustive Glycosylation, PEGylation, and Glutathionylation of a [G4]-ene(48) Dendrimer via Photoinduced Thiol-ene Coupling
- 2011
-
In: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 49:20, s. 4468-4475
-
Journal article (peer-reviewed)abstract
- The use of free-radical thiol-ene coupling (TEC) for the introduction of carbohydrate, poly(ethylene glycol), and peptide fragments at the periphery of an alkene functional dendrimer has been reported in this article. Four different sugar thiols including glucose, mannose, lactose, and sialic acid, two PEGylated thiols, and the natural tripeptide glutathione were reacted with a fourth generation alkene functional dendrimer [G4]-ene(48) on irradiation at lambda(max) 365 nm. In all cases, the (1)H NMR spectra of the crude reaction mixture revealed the complete disappearance of alkene proton signals indicating the quantitative conversion of all 48 alkene groups of the dendrimer. With one exception only, all dendrimer conjugates were isolated in high yields (70-94%), validating the high efficiency of multiple TEC reactions on a single substrate. All isolated and purified compounds were analyzed by matrix assisted laser desorption ionization-time of flight (MALDI-TOF) spectrometry and gave spectra consistent with the assigned structure.
|
|
