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1.
Mater Sci Eng C Mater Biol Appl ; 116: 111109, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32806230

ABSTRACT

Implant-associated infections present severe and difficult-to-treat complications after surgery, related to implant biofilm colonization. Systemic administration of antibiotics cannot reach sufficient concentrations at the infected site and may be toxic. Here we describe how mussel-inspired dendritic material coated on a titanium surface can locally activate a prodrug of daptomycin (pro-dapto) to treat methicillin-resistant Staphylococcus aureus. The mechanism of the prodrug activation is based on bio-orthogonal click chemistry between a tetrazine (Tz) and trans-cyclooctene (TCO). The former is attached to the dendritic polymer, while the later converts daptomycin into a prodrug. Characterization of the material's properties revealed that it is hydrophobic, non-toxic, and stable for a prolonged period of time. We envision that the titanium coated dendritic material will be able to improve the treatment of implant-associated infections by concentrating systemically administered antibiotic prodrugs, thus converting them into active localized medicines.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Biofilms , Coated Materials, Biocompatible/pharmacology , Humans , Polymers , Staphylococcal Infections/drug therapy , Titanium/pharmacology
2.
ACS Appl Bio Mater ; 2(12): 5749-5759, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-35021568

ABSTRACT

Biofouling constitutes a major challenge in the application of biosensors and biomedical implants, as well as for (food) packaging and marine equipment. In this work, an antifouling surface coating based on the combination of mussel-inspired dendritic polyglycerol (MI-dPG) and an amine-functionalized block copolymer of linear polyglycerol (lPG-b-OA11, OA = oligo-amine) was developed. The coating was compared to a MI-dPG surface which was postfunctionalized with commercially available amine-terminated polyethylene glycol (HO-PEG-NH2) of similar molecular weight. In the current work, these coatings were compared in their chemical stability, protein fouling characteristics, and cell fouling characteristics. The lPG-b-OA11-functionalized coating showed high chemical stability in both phosphate buffered saline (PBS) and sodium dodecyl sulfate (SDS) solutions and reduced the adhesion of fibrinogen from human plasma with 99% and the adhesion of human serum albumin with 96%, in comparison to the bare titanium dioxide substrate. Furthermore, the proliferation of human umbilical vein endothelial cells (HUVECs) was reduced with 85% when the lPG-b-OA11 system was compared to bare titanium dioxide. Additionally, a reduction of 94% was observed when the lPG-b-OA11 system was compared to tissue culture polystyrene.

3.
Chemistry ; 20(42): 13527-30, 2014 Oct 13.
Article in English | MEDLINE | ID: mdl-25168197

ABSTRACT

Here we demonstrate that deracemization of isoindolinones using Viedma ripening is possible starting from a racemic mixture of conglomerate crystals. Crystals of the enantiopure isoindolinones lose their chiral identity upon dissolution even without the need for a catalyst. This enabled complete deracemization of the reported isoindolinones without a catalyst.


Subject(s)
Isoindoles/chemistry , Crystallization , Solubility , Stereoisomerism
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