Predicting human pharmacokinetics of liposomal temoporfin using a hybrid in silico model.

Over the years, the performance of the liposomal formulations of temoporfin, Foslip® and Fospeg®, was investigated in a broad array of cell-based assays and preclinical animal models. So far, little attention has been paid to the influence of drug release and liposomal stability on the plasma concentration-time profile. The drug release is a key attribute which impacts product quality and the in vivo efficacy of nanocarrier formulations.

A new level of in vivo singlet molecular oxygen luminescence measurements.

Background: Singlet oxygen is known to be the main mediator of the photodynamic effect. The kinetics of its generation and deactivation allows for insights in the microenvironment and efficacy of the photodynamic effect. Therefore, it is highly desirable to perform direct and time resolved measurements of singlet molecular oxygen (O) as well as data analysis during the therapy.

Flow cytometry-based FRET identifies binding intensities in PPARγ1 protein-protein interactions in living cells.

PPARγ is a pharmacological target in inflammatory and metabolic diseases. Upon agonistic treatment or following antagonism, binding of co-factors is altered, which consequently affects PPARγ-dependent transactivation as well as its DNA-independent properties. Therefore, establishing techniques to characterize these interactions is an important issue in living cells.

Mosquito larvae control by photodynamic inactivation of their intestinal flora - a proof of principal study on Chaoborus sp.

Mosquitoes are carriers of dangerous infectious disease pathogens all over the world. Owing to travelling and global warming, tropical disease-carrying species such as Aedes, Anopheles and Culex spread beyond tropical and subtropical zones, even to Europe. The aim of this study is to investigate the potential of photodynamic agents to combat mosquito larvae.

Advanced in silico modeling explains pharmacokinetics and biodistribution of temoporfin nanocrystals in humans.

Foscan®, a formulation comprising temoporfin dissolved in a mixture of ethanol and propylene glycol, has been approved in Europe for palliative photodynamic therapy of squamous cell carcinoma of the head and neck. During clinical and preclinical studies it was observed that considering the administration route, the drug presents a rather atypical plasma profile as plasma concentration peaks delayed. Possible explanations, as for example the formation of a drug depot or aggregation after intravenous administration, are discussed in current literature.

In vitro photodynamic inactivation (PDI) of pathogenic germs inducing onychomycosis.

Onychomycosis is a fungal nail infection caused primarily by the dermatophytes Trichophyton rubrum and Trichophyton interdigitale or, less frequently, by molds like Aspergillus spp. and Scopulariopsis brevicaulis. Photodynamic treatment of onychomycosis is considered a promising future therapy to overcome the frequent failure of currently used antifungals.

Electron beam functionalized photodynamic polyethersulfone membranes - photophysical characterization and antimicrobial activity.

Polymer membranes are powerful filtration tools in medicine and water treatment. Their efficiency and operational lifetime is limited by biofouling caused by microorganisms. This study describes the development of photodynamical active antimicrobial polymer membranes in a one-pot functionalization step using a well-known photosensitizer (PS).

In vivo singlet molecular oxygen measurements: Sensitive to changes in oxygen saturation during PDT.

Background: Direct singlet molecular oxygen detection is known to be a valuable tool for understanding photodynamic action. It could become useful for optimizing illumination schedules in photodynamic therapy. The method of time resolved singlet molecular oxygen luminescence detection can give insights into generation of singlet oxygen and its interaction with the environment and therefore possibly allows monitoring the treatments efficacy.

Photodynamic inactivation of Escherichia coli - Correlation of singlet oxygen kinetics and phototoxicity.

Photodynamic inactivation (PDI) of bacteria may play a major role in facing the challenge of the ever expanding antibiotic resistances. Here we report about the direct correlation of singlet oxygen luminescence kinetics and phototoxicity in E. coli cell suspension under PDI using the widely applied cationic photosensitizer TMPyP.

Synthesis, Photophysics and PDT Evaluation of Mono-, Di-, Tri- and Hexa-PEG Chlorins for Pointsource Photodynamic Therapy.

Pointsource photodynamic therapy (PSPDT) is a newly developed fiber optic method aimed at the delivery of photosensitizer, light and oxygen to a diseased site. Because of a need for developing photosensitizers with desirable properties for PSPDT, we have carried out a synthetic, photophysical and phototoxicity study on a series of PEGylated sensitizers. Chlorin and pheophorbide sensitizers were readily amenable to our synthetic PEGylation strategy to reach triPEG and hexaPEG galloyl pheophorbides and mono-, di-, triPEG chlorins.

Photodynamic inactivation of biofilm building microorganisms by photoactive facade paints.

This study was performed as a proof of concept for singlet oxygen generating facade paint as an alternative to conventional biocide containing facade paint for the prevention of biofilm growth on outdoor walls. Biofilms on outdoor walls cause esthetic problems and economic damage. Therefore facade paints often contain biocides.

Photodynamic inactivation of mold fungi spores by newly developed charged corroles.

The photodynamic effect, originally used in photodynamic therapy (PDT) for the treatment of different diseases, e.g. of cancer, has recently been introduced for the inactivation of bacteria.

Photosensitizer loaded HSA nanoparticles II: in vitro investigations.

The photosensitizing efficiency of human serum albumin (HSA) nanoparticles loaded with the photosensitizers meta-tetra(hydroxy-phenyl)-chlorin (mTHPC) and meta-tetra(hydroxy-phenyl)-porphyrin (mTHPP) was investigated in vitro. The endocytotic intracellular uptake, and the time dependent drug release caused by nanoparticle decomposition of the PS loaded HSA nanoparticles were studied on Jurkat cells in suspension. The photoxicity as well as the intracellular singlet oxygen ((1)O(2)) generation were investigated in dependence on the incubation time.

Photosensitizer loaded HSA nanoparticles. I: Preparation and photophysical properties.

Photodynamic therapy (PDT) is a promising option in the treatment of cancer. Efficient photosensitizers are available but many of them have insufficient physico-chemical properties for parenteral application. We have established nanoparticles consisting of human serum albumin (HSA) as a drug carrier system for 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrine (mTHPP) and 5,10,15,20-tertrakis(m-hydroxyphenyl)chlorin (mTHPC), two well-known photosensitizers.

New insights to primary photodynamic effects--Singlet oxygen kinetics in living cells.

The kinetics of chemical singlet oxygen quencher consumption inside living cells during low dose illumination was revealed via time resolved singlet oxygen luminescence detection. Deviations of the measured data from the common theoretical model for (1)O(2) kinetics forced the authors to consider a one-dimensional diffusion model for description of the kinetics of singlet oxygen generated by membrane localized photosensitizers. Our observations reconcile seemingly contradictory reports presenting different values for the efficiency of singlet oxygen interaction with cells.

Novel photosensitizer-protein nanoparticles for photodynamic therapy: photophysical characterization and in vitro investigations.

In this work two types of pheophorbide-HSA (Pheo-HSA) nanoparticles, PHSA40 and PHSA100, were prepared and their photophysical and photosensitizing properties were investigated. Due to intramolecular interactions the singlet oxygen quantum yield of PHSA40 and PHSA100 is very low (less than 0.1).