Nordic Institute of Dental Materials NIOM As

Norway

Nordic Institute of Dental Materials NIOM As

Norway
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Haukvik T.,University of Oslo | Haukvik T.,Nordic Institute of Dental Materials NIOM As | Bruzell E.,University of Oslo | Bruzell E.,Nordic Institute of Dental Materials NIOM As | And 4 more authors.
Pharmazie | Year: 2011

Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, has potential as a photosensitiser for photodynamic treatment of localised superficial infections in e.g., the mouth or skin. The aim of the present study was to evaluate the in vitro antibacterial phototoxic potential of a series of five curcumin derivatives. The gram-positive Enterococcus faecalis and the gram-negative Escherichia coli were used as bacterial models. The bacteria were exposed to curcuminoid preparations in two concentrations (2.5 and 25.0μM) in combination with a constant irradiation dose (5 J/cm 2). The UV-VIS absorption spectrum of the curcuminoids was in the same range as curcumin, 300-500 nm. Compound 1 (dimethoxycurcumin; C1) and compound 3 (bisdemethoxycurcumin; C3) were strongly phototoxic towards E. faecalis (no surviving bacteria) and showed a lower but significant effect towards E. coli (≤ 0.5 log reductions and 1-4 log reductions, respectively). Compound 2 (C2) and compound 4 (C4) in combination with blue light reduced the colony forming ability of E. faecalis (∼1-4 log reductions). The phototoxic effect of the curcuminoids varied with concentration, and for compounds C1, C2 and C3 it was further influenced by the addition of polyethylene glycol 400 (PEG 400) to the preparations. 2,6 - Divanillylidenecyclohexanone (C5) showed very low phototoxic potential (<0.2 log reductions) under the conditions used in the present study. The addition of polyethylene glycol 400 (PEG 400) seemed to increase the solubility of compound C1, C3 and C5 in phosphate buffered saline (PBS). This investigation demonstrates the importance and influence of the substituents on the phenolic rings and the keto-enol moiety for the phototoxic potential of curcumin and its derivatives.


Hegge A.B.,University of Oslo | Hegge A.B.,Nordic Institute of Dental Materials NIOM As | Bruzell E.,Nordic Institute of Dental Materials NIOM As | Kristensen S.,University of Oslo | Tonnesen H.H.,University of Oslo
European Journal of Pharmaceutical Sciences | Year: 2012

Solubilization and stabilization from rapid degradation by the use of nanocarriers are necessary to exploit curcumin's phototoxic potential towards pathogenic bacteria. However, maintenance of the phototoxicity requires a careful selection of type and amount of nanocarrier. The phototoxicity of an aqueous supersaturated curcumin solution without nanocarrier was compared to that of curcumin solubilized in polyethylene glycol 400 (PEG 400), Pluronic® F 127 (F 127) and hydroxypropyl-γ-cyclodextrin (HPγCD) on Staphylococcus (S.) epidermidis biofilms and suspensions. The nanocarriers stabilized the hydrophobic photosensitizer (PS) towards physical precipitation and hydrolytic degradation; however, photobleaching was pronounced (46-100% degradation) after irradiation with a dose of ∼9 J/cm2 blue light depending on selected nanocarrier. Complete inactivation of S. epidermidis in suspension was achieved after exposure of ∼5 J/cm2 combined with curcumin in 20% PEG 400 and 0.5% HPγCD and less than 1 J/cm2 light in case of a supersaturated curcumin solution. Curcumin in 1.5% F 127 induced phototoxicity towards bacterial biofilms; however, it was not phototoxic towards planktonic S. epidermidis. All curcumin preparations investigated demonstrated significant and similar phototoxicity towards biofilms (13-29% bacterial survival). A ∼9 J/cm2 light dose was not sufficient to eradicate S. epidermidis biofilm completely under the current conditions. © 2012 Elsevier B.V. All rights reserved.


Hegge A.B.,University of Oslo | Vukicevic M.,University of Oslo | Bruzell E.,Nordic Institute of Dental Materials NIOM As | Kristensen S.,University of Oslo | Tonnesen H.H.,University of Oslo
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

Curcumin is under investigation as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The therapeutic potential of curcumin as a PS is limited by its low aqueous solubility, susceptibility to hydrolytic and photolytic degradation, and limited phototoxicity toward Gram negative (G-) bacteria. Supersaturated solutions of curcumin have demonstrated high phototoxicity toward several species of Gram positive (G+) bacteria as well as the G- Escherichia (E) coli. Thus, solid dispersions that can form supersaturated solutions of curcumin upon hydration may be beneficial in aPDT. In the present study, solid dispersions of curcumin have been prepared through lyophilization of concentrated solutions obtained from dissolution of hydroxypropyl-β-cyclodextrin (HPβCD)-curcumin co-precipitates. Hydroxypropyl methylcellulose (HPMC) was added to curcumin solutions prior to lyophilization. The resulting lyophilizates were porous, amorphous and hydrated and dissolved rapidly in contact with a model physiological salt solution. The detected drug load of the lyophilizates was in the range 0.5-1.0% (w/w) and was dependent on the selected ratio between HPβCD and curcumin in the co-precipitate. The lyophilizate with the highest drug load could easily be dissolved in aqueous medium to form curcumin solutions of relevant concentrations for aPDT (i.e., 10 μM). Selected solutions of the curcumin solid dispersions showed a pronounced decrease in curcumin concentration up to 90% after storage for 168 h, which indicated that supersaturated curcumin solutions were initially formed upon dissolution of the lyophilizates. Both freshly prepared and 2 days old solutions of one selected curcumin lyophilizate induced significant inactivation of E. coli (∼1% bacterial survival) after exposure to a light dose of only 5 J/cm2. © 2012 Elsevier B.V. All rights reserved.


Westas E.,Chalmers University of Technology | Westas E.,Nordic Institute of Dental Materials NIOM As | Gillstedt M.,Sahlgrenska University Hospital | Lonn-Stensrud J.,University of Oslo | And 2 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2014

Biofilm formation on medical devices is a common cause of implant failure, especially regarding implants that breach the epithelial tissue, so-called transcutaneous implants. Nanotechnology and the development of new nanomaterials have given the opportunity to design nanotextured implant surfaces. Such surfaces have been studied using various in vitro methods showing that nanosized features strongly benefit bone cell growth. However, little is known on how nanostructured features affect biofilm formation. The aim of this study was therefore to examine the shape- and chemical-dependent effect of a nanostructured hydroxyapatite (HA) coating on the degree of Staphylococcus epidermidis biofilm formation. Three different types of nanosized HA particles having different shapes and calcium to phosphate ratios were compared to uncoated turned titanium using safranin stain in a biofilm assay and confocal laser scanning microscopy (CLSM) for assessment of biofilm biomass and bacterial volume, respectively. No difference in biofilm biomass was detected for the various surfaces after 6 h incubation with S. epidermidis. Additionally, image analysis of CLSM Z-stacks confirmed the biofilm assay and showed similar results. In conclusion, the difference in nanomorphology and chemical composition of the surface coatings did not influence the adhesion and biofilm formation of S. epidermidis. © 2013 Wiley Periodicals, Inc.

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