Using effective medium theories to design tailored nanocomposite materials for optical systems

Modern optical systems are subject to very restrictive performance, size and cost requirements. Especially in portable systems size often is the most important factor, which necessitates elaborate designs to achieve the desired specifications. However, current designs already operate very close to the physical limits and further progress is difficult to achieve by changing only the complexity of the design. Another way of improving the performance is to tailor the optical properties of materials specifically to the application at hand. A class of novel, customizable materials that enables the tailoring of the optical properties, and promises to overcome many of the intrinsic disadvantages of polymers, are nanocomposites. However, despite considerable past research efforts, these types of materials are largely underutilized in optical systems. To shed light into this issue we, in this paper, discuss how nanocomposites can be modeled using effective medium theories. In the second part, we then investigate the fundamental requirements that have to be fulfilled to make nanocomposites suitable for optical applications, and show that it is indeed possible to fabricate such a material using existing methods. Furthermore, we show how nanocomposites can be used to tailor the refractive index and dispersion properties towards specific applications.Comment: This is a draft manuscript of a paper published in Proc. SPIE (Proceedings Volume 10745, Current Developments in Lens Design and Optical Engineering XIX, Event: SPIE Optical Engineering + Applications, 2018

Evaluation of a luminometric cell counting system in context of antimicrobial photodynamic inactivation

Antimicrobial resistance belongs to the most demanding medical challenges, and antimicrobial photodynamic inactivation (aPDI) is considered a promising alternative to classical antibiotics. However, the pharmacologic characterization of novel compounds suitable for aPDI is a tedious and time-consuming task that usually requires preparation of bacterial cultures and counting of bacterial colonies. In this study, we established and utilized a luminescence-based microbial cell viability assay to analyze the aPDI effects of two porphyrin-based photosensitizers (TMPyP and THPTS) on several bacterial strains with antimicrobial resistance. We demonstrate that after adaptation of the protocol and initial calibration to every specific bacterial strain and photosensitizer, the luminometric method can be used to reliably quantify aPDI effects in most of the analyzed bacterial strains. The interference of photosensitizers with the luminometric readout and the bioluminescence of some bacterial strains were identified as possible confounders. Using this method, we could confirm the susceptibility of several bacterial strains to photodynamic treatment, including extensively drug-resistant pathogens (XDR). In contrast to the conventional culture-based determination of bacterial density, the luminometric assay allowed for a much more time-effective analysis of various treatment conditions. We recommend this luminometric method for high-throughput tasks requiring measurements of bacterial viability in the context of photodynamic treatment approaches

Design rules for customizable optical materials based on nanocomposites

Nanocomposites with tailored optical properties can provide a new degree of freedom for optical design. However, despite their potential these materials remain unused in bulk applications. Here we investigate the conditions under which they can be used for optical applications using Mie theory, effective medium theories, and numerical simulations based on the finite element method. We show that due to scattering different effective medium regimes have to be distinguished, and that bulk materials can only be realized in a specific parameter range. Our analysis also enables us to quantify the range of validity of different effective medium theories, and identify design rules on how the free material parameters should be adjusted for specific applications.Comment: 13 pages, 6 figure

Photosensitizer-loaded hydrogels for photodynamic inactivation of multirestistant bacteria in wounds

Photodynamic treatment is a promising tool for the therapy of multidrug-resistant bacteria. In this study, we highlight photosensitizer-loaded hydrogels as an application system for infected wounds. The poly(ethylene glycol) diacrylate-based and electron beam-polymerized hydrogels were mechanically stable and transparent. They were loaded with two photoactive, porphyrin-based drugs – tetrakis(1 methylpyridinium-4-yl)porphyrin p-toluenesulfonate (TMPyP) and tetrahydroporphyrin – p toluenesulfonate (THPTS). The hydrogels released a sufficient amount of the photosensitizers (up to 300 μmol l(−1)), relevant for efficiency. The antimicrobial effectivity of loaded hydrogels was investigated in a tissue-like system as well as in a liquid system against a multiresistant Escherichia coli. In both systems, light induced eradication was possible. In contrast, hydrogels alone showed only minor antimicrobial activity. Furthermore, the loaded hydrogels were successfully tested against seven multidrug-resistant bacterial strains, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Achromobacter xylosoxidans. The eradication of these pathogens, except A. xylosoxidans, was successfully demonstrated. In general, TMPyP-loaded hydrogels were more effective than THPTS-loaded ones. Nevertheless, both photosensitizers displayed effectivity against all investigated bacteria strains. Taken together, our data demonstrate that photosensitizer-loaded hydrogels are a promising new tool to improve the treatment of wounds infected with problematic bacterial pathogens

Photodynamic inactivation of SARS-CoV-2 infectivity and antiviral treatment effects in vitro

Despite available vaccines, antibodies and antiviral agents, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic still continues to cause severe disease and death. Current treatment options are limited, and emerging new mutations are a challenge. Thus, novel treatments and measures for prevention of viral infections are urgently required. Photodynamic inactivation (PDI) is a potential treatment for infections by a broad variety of critical pathogens, including viruses. We explored the infectiousness of clinical SARS-CoV-2 isolates in Vero cell cultures after PDI-treatment, using the photosensitizer Tetrahydroporphyrin-tetratosylate (THPTS) and near-infrared light. Replication of viral RNA (qPCR), viral cytopathic effects (microscopy) and mitochondrial activity were assessed. PDI of virus suspension with 1 µM THPTS before infection resulted in a reduction of detectable viral RNA by 3 log levels at day 3 and 6 after infection to similar levels as in previously heat-inactivated virions (<99.9%; p < 0.05). Mitochondrial activity, which was significantly reduced by viral infection, was markedly increased by PDI to levels similar to uninfected cell cultures. When applying THPTS-based PDI after infection, a single treatment had a virus load-reducing effect only at a higher concentration (3 µM) and reduced cell viability in terms of PDI-induced toxicity. Repeated PDI with 0.3 µM THPTS every 4 h for 3 d after infection reduced the viral load by more than 99.9% (p < 0.05), while cell viability was maintained. Our data demonstrate that THPTS-based antiviral PDI might constitute a promising approach for inactivation of SARS-CoV-2. Further testing will demonstrate if THPTS is also suitable to reduce the viral load in vivo

The meta-substituted isomer of TMPyP enables more effective photodynamic bacterial inactivation than para-TMPyP in vitro

Porphyrinoid-based photodynamic inactivation (PDI) provides a promising approach to treating multidrug-resistant infections. However, available agents for PDI still have optimization potential with regard to effectiveness, toxicology, chemical stability, and solubility. The currently available photosensitizer TMPyP is provided with a para substitution pattern (para-TMPyP) of the pyridinium groups and has been demonstrated to be effective for PDI of multidrug-resistant bacteria. To further improve its properties, we synthetized a structural variant of TMPyP with an isomeric substitution pattern in a meta configuration (meta-TMPyP), confirmed the correct structure by crystallographic analysis and performed a characterization with NMR-, UV/Vis-, and IR spectroscopy, photostability, and singlet oxygen generation assay. Meta-TMPyP had a hypochromic shift in absorbance (4 nm) with a 55% higher extinction coefficient and slightly improved photostability (+6.9%) compared to para-TMPyP. Despite these superior molecular properties, singlet oxygen generation was increased by only 5.4%. In contrast, PDI, based on meta-TMPyP, reduced the density of extended spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli by several orders of magnitude, whereby a sterilizing effect was observed after 48 min of illumination, while para-TMPyP was less effective (p < 0.01). These findings demonstrate that structural modification with meta substitution increases antibacterial properties of TMPyP in PDI