Biolitec (Germany)

Abstract Complex service innovations constitute a cornerstone in the strategy of numerous industrial companies. The industrial sales force assumes an important role in the selling of these complex service innovations. For firms a key challenge in this respect resides in ensuring the sales force's motivation for the selling of such innovations and effectively solving customers’ business problems. Past research frequently discussed monetary sales incentives as an effective tool to reinforce desired employee behaviors, but, to date, the discussion has failed to produce conclusive guidance for practitioners as to whether monetary sales incentives in fact can facilitate selling of complex service innovations. To clarify the effects of monetary sales incentives in this respect, we draw on self‐focus theory to disentangle how complex service innovation selling is shaped by the interplay of salesperson service incentives (i.e., the extent to which variable compensation depends on service turnover) and salesperson share of variable compensation (i.e., the percentage of compensation that depends on performance). To test these interactive effects, we use a multiple‐source data set including 294 salespeople, and match objective firm data. The results reveal that when service incentives are high, the share of variable compensation exhibits an inverse u‐shaped effect on a salesperson's problem‐solving behavior, which is an important predictor of innovative service selling success. In addition, the share of variable compensation increases work effort, which in turn drives innovative service selling success. These findings shed light on the intricate “human”, employee‐related side of service innovation management and provide actionable implications for managers how to increase their firms’ innovative service selling success.

The absorption properties of Temoporfin, a second-generation photosensitizer employed in photodynamic therapy, are calculated with an electrostatic-embedding quantum mechanics/molecular mechanics (QM/MM) scheme in methanol. The suitability of several ensembles of geometries generated by different sampling techniques, namely classical-molecular-dynamics (MD) and QM/MM-MD thermal sampling, Wigner quantum sampling and a hybrid protocol, which combines the thermal and quantum approaches, is assessed. It is found that a QM description of the chromophore during the sampling is needed in order to achieve a good agreement with respect to the experimental spectrum. Such a good agreement is obtained with both QM/MM-MD and Wigner samplings, demonstrating that a proper description of the anharmonic motions of the chromophore is not relevant in the computation of the absorption properties. In addition, it is also found that solvent organization is a rather fast process and a long sampling is not required. Finally, it is also demonstrated that the same exchange-correlation functional should be employed in the sampling and in the computation of the excited states properties to avoid unphysical triplet states with relative energies close or below 0 eV.

Abstract The copper(I)‐catalyzed 1,3‐dipolar cycloaddition of 4‐azido(tetrafluorophenyl)boron‐dipyrrin (azido‐BODIPY) with diverse terminal alkynes, varying from simple alkyl‐substituted derivatives to alkynes with functional groups and carbohydrates, was successfully employed to obtain meso‐functionalized BODIPY derivatives through the 1,2,3‐triazole linkage. The scope of this reaction was extended to the preparation of di‐ and trivalent BODIPY systems through the use of appropriate alkynyl linkers. Moreover, the synthesis of hydroxyl‐ and pentafluorothio‐(SF5)‐substituted, 1,2,3‐triazole‐linked array systems consisting of porphyrins and corroles as the central scaffold, in combination with a BODIPY, was investigated. These covalently connected tetrapyrrole‐BODIPY arrays exemplify a versatile approach to the construction of multichromophore systems: the combination of 1,3‐dipolar cycloaddition and nucleophilic substitution on pentafluorophenyl‐substituted porphyrinoids. The systems designed herein could serve in various light‐harvesting applications and electron‐transfer studies.

Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process. Polymeric nanoparticles were prepared by nanoprecipitation of Eudragit® RS 100 in presence and in absence of glycofurol. The photosensitizer temoporfin has been encapsulated into these carrier devices. Process parameters were optimized by means of a Design of Experiments approach and nanoparticles with optimal characteristics were manufactured by using microreactor technology. The efficacy was determined by means of cell culture models in A-253 cells. Physicochemical properties of nanoparticles achieved by nanoprecipitation from ethanolic solutions were superior to those obtained from a method based upon glycofurol. Nanoencapsulation of temoporfin into the matrix significantly reduced toxicity of this compound, while the efficacy was maintained. The release profiles assured a sustained release at the site of action. Finally, the transfer to continuous flow technology was achieved. By adjusting all process parameters, a potent formulation for application in the GI tract was obtained. The essential steps of process development and scale-up were part of this formulation development.

Fospeg® is a newly developed photosensitizer formulation based on meso-tetra(hydroxyphenyl)chlorin (mTHPC), with hydrophilic liposomes to carry the hydrophobic photosensitizer to the target tissue. In this study the pharmacokinetics and biodistribution of Fospeg® were investigated by high performance liquid chromatography at various times (0.5-18 hours) following systemic i.v. administration. As a model an experimental HT29 colon tumor in NMRI nu/nu mice was employed. Our study indicates a higher plasma peak concentration, a longer circulation time and a better tumor-to-skin ratio than those of Foslip®, another liposomal mTHPC formulation. Data from ex vivo tissue fluorescence and reflectance imaging exhibit good correlation with chemical extraction. Our results have shown that optical imaging provides the potential for fluorophore quantification in biological tissues.

The folate receptor (FR) is over-expressed in many human tumours and is being intensively studied also in the field of nanomedicine as a target to enhance the selectivity of drug delivery to cancer cells by using nanocarriers bearing folic acid (FA) on their surface. In this study we report the encapsulation of the photosensitizer (PS) meta-tetra(hydroxyphenyl)chlorin (m-THPC) in FA-targeted PEGylated liposomes used as a novel drug delivery system for photodynamic therapy (PDT) of cancer. Our in vitro investigations revealed that only a modest fraction of targeted liposomes were internalized by specific endocytosis in FR-positive KB cells. However, FA-liposomes doubled the uptake of the entrapped m-THPC with respect to un-targeted liposomes and enhanced the photo-induced cytotoxicity in KB cells. In contrast, in FR-negative A549 cells FA-targeted or un-targeted liposomes exhibited a very similar extent of internalization and as a consequence the same photo-killing efficiency.

Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.