| 1. |
- Andrén, Oliver C. J., et al.
(författare)
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Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
- 2019
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659.
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Tidskriftsartikel (refereegranskat)abstract
- A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.
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| 2. |
- Nordström, Randi, 1986-, et al.
(författare)
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Degradable dendritic nanogels as carriers for antimicrobial peptides
- 2019
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 554, s. 592-602
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40–60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 µM.
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| 3. |
- Rozenbaum, Rene T., et al.
(författare)
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Penetration and Accumulation of Dendrons with Different Peripheral Composition in Pseudomonas aeruginosa Biofilms
- 2019
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 19:7, s. 4327-4333
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Tidskriftsartikel (refereegranskat)abstract
- Multidrug resistant bacterial infections threaten to become the number one cause of death by the year 2050. Development of antimicrobial dendritic polymers is considered promising as an alternative infection control strategy. For antimicrobial dendritic polymers to effectively kill bacteria residing in infectious biofilms, they have to penetrate and accumulate deep into biofilms. Biofilms are often recalcitrant to antimicrobial penetration and accumulation. Therefore, this work aims to determine the role of compact dendrons with different peripheral composition in their penetration into Pseudomonas aeruginosa biofilms. Red fluorescently labeled dendrons with pH-responsive NH3+ peripheral groups initially penetrated faster from a buffer suspension at pH 7.0 into the acidic environment of P. aeruginosa biofilms than dendrons with OH or COO- groups at their periphery. In addition, dendrons with NH3+ peripheral groups accumulated near the top of the biofilm due to electrostatic double-layer attraction with negatively charged biofilm components. However, accumulation of dendrons with OH and COO- peripheral groups was more evenly distributed across the depth of the biofilms than NH3+ composed dendrons and exceeded accumulation of NH3+ composed dendrons after 10 min of exposure. Unlike dendrons with NH3+ groups at their periphery, dendrons with OH or COO- peripheral groups, lacking strong electrostatic double-layer attraction with biofilm components, were largely washed-out during exposure to PBS without dendrons. Thus, penetration and accumulation of dendrons into biofilms is controlled by their peripheral composition through electrostatic double-layer interactions, which is an important finding for the further development of new antimicrobial or antimicrobial-carrying dendritic polymers.
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| 4. |
- Zhang, Yuning, et al.
(författare)
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Off-Stoichiometric Thiol-Ene Chemistry to Dendritic Nanogel Therapeutics
- 2019
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Ingår i: Advanced Functional Materials. - : Wiley-VCH Verlag. - 1616-301X .- 1616-3028. ; 29:18
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Tidskriftsartikel (refereegranskat)abstract
- A novel platform of dendritic nanogels is herein presented, capitalizing on the self-assembly of allyl-functional polyesters based on dendritic-linear-dendritic amphiphiles followed by simple cross-linking with complementary monomeric thiols via UV initiated off-stoichiometric thiol-ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190–295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.
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