After peaking, the concentrations dropped with half-lives between 3.5 and 9.3 h but did not reach the initial levels within 18 h again. Compared to pre-training levels, the increase in metabolite excretion was between 546-933 %. During peak excretion reference values for hydroxynaphthalene (35 μg/L, sum of 1- and 2-isomer) and 1-hydroxypyrene (0.30 μg/L) were exceeded in 64 % (maximum 381.3 μg/L) and 73 % of the samples (maximum 1.88 μg/g crea.), respectively. Live fire training is associated with an additional uptake of PAH. Due to the consequent use of SCBA, dermal absorption is assumed as major exposure route. Further measures to reduce PAH exposure should be considered, in particular since higher internal loads caused by accumulation effects are to be expected with daily or more frequent training.Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency 3,4-DMMC >> MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.Chronic kidney disease (CKD) is one of the leading public health problems worldwide and finally progresses to end-stage renal disease. The therapeutic options of CKD are very limited. Thus, development of drug delivery systems specific-targeting to kidney may offer more options. Here we developed an efficient kidney-targeted drug delivery system using a FITC labeled renal tubular-targeting peptide modified PLGA-PEG nanoparticles and investigated the intrarenal distribution and cell-type binding. We found that the modified nanoparticles with an approximate diameter of 200 nm exhibited the highest binding capacity with HK-2 cells and fluorescence and immunohistochemical analysis showed they mainly localized in renal proximal tubules by passing through the basolateral side. Furthermore, these kidney-specific nanoparticles could significantly enhance the therapeutic effects of asiatic acid, an insoluble triterpenoid compound as drug delivery carriers. In conclusion, these results suggest the potential of the peptide modified PLGA-PEG nanoparticles as kidneytargeted drug delivery system to proximal tubular cells in treatment of CKD.The aim of this study was to prepare and evaluate simvastatin (SIM) loaded elastic provesicular systems for effective topical wound management. SIM provesicles were prepared using the non-ionic surfactant Span 40, cholesterol and three edge activators i.e. XMU-MP-1 concentration Span 80, Tween 80 and sodium cholate. The vesicles revealed high SIM encapsulation efficiency ranging from 87.25 to 98.15%, whereas vesicle sizes ranged from 462.3 to 801.5 nm. Vesicle sizes decreased with increasing the concentration of the edge activator. High negative zeta potential values were observed, revealing good stability of the vesicular formulations. The release of SIM from hydrated provesicular carriers was biphasic in nature. The selected SIM provesicular elastic carrier exerted approximately two-fold increase in the amount of SIM permeated through rat skin, compared to the free drug. Evaluation of wound healing activity of the selected provesicular formulation revealed significant reduction in wound size in rats, fourteen days post-wounding. These results were further confirmed by a significant increase in expression of vascular endothelial growth factor and collagen type I compared to the free drug. These results indicate that provesicular carriers could be a promising drug delivery system for encapsulating SIM and enhancing its wound healing efficacy.Dexamethasone release from natural γ-cyclodextrin (γCD) complexes was investigated in presence of porcine pancreatic α-amylase (PPA). The phase-solubility of dexamethasone in aqueous γCD solutions was determined, PPA degradation of γCD was investigated, and permeation studies were performed in simulated tear fluid. The phase-solubility profile was of Bs type and the stability constant (K11) of the dexamethasone/γCD complex determined from the initial linear section of the profile was relatively high or 12887 M-1. The high K11 value indicates that dexamethasone has high affinity for γCD under the test condition. From the PPA catalyzed γCD degradation studies the Michaelis-Menten constant (Km) and Vmax were determined to be 3.24 mM and 9.79 × 10-3 mM/min, respectively. The permeation studies performed at low γCD concentrations, showed that dexamethasone is released from the complex solutions at faster rate when PPA was present than when no PPA was present.This study focuses on the fate of excipients contained in topical emulsions once applied on the skin. The aim was thus to develop a methodology to characterize the residue left on the skin shortly after emulsion application. To this end, both the role and the impact of the different excipients on the formation and properties of the residue left on the skin surface once a product is applied were investigated. To that purpose, an O/W emulsion composed of an ester as oily phase, an emulsifier (alkylpolyglucoside-based vehicles), a polymer and a humectant (hydrophilic excipient) was first developed. Then, systems with fewer ingredients were prepared to understand their respective role in the residual film. This residual film was studied in vivo by means of biophysical instrumental methods, all being performed on the participants’ forearm. Results highlighted the major role of the ester giving a bright and hydrophobic residue. While the surfactant structuration as the presence of glycerin and polymer provided a specific water distribution inside the residue on the skin surface.