Conjugation
of antibiotics
with polymers is an emerging strategy to improve the performance of
these important drugs. Here, the antibiotic ciprofloxacin (CIP) was
conjugated with amphiphilic poly(2-oxazoline) (POx) block copolymers
to investigate whether the activity of the antibiotic was enhanced
due to additionally induced membrane activity. The resulting polymer–antibiotic
conjugates (PACs) are an order of magnitude more active against the
bacterial strain Staphylococcus aureus than CIP and show high activities against numerous pathogenic bacterial
strains. Their high activity depends on an optimal hydrophobic/hydrophilic
balance (HHB) of the POx tail. Mechanistic studies revealed that the
derivatization of CIP required for the polymer conjugation lowers
the affinity of the antibiotic to its target topoisomerase IV. However,
the amphiphilic PACs are most likely concentrated within the bacterial
cytoplasm, which overcompensates the loss of affinity and results
in high antibacterial activity. In addition, the development of resistance
in S. aureus and Escherichia
coli is slowed down. More importantly, the amphiphilic
PACs are active against CIP-resistant S. aureus and E. coli. The PACs with the highest
activity are not cytotoxic toward human stem cells and do not lyse
blood cells in saturated solution.
This book analyses the provision of personnel in the context of a mixed contract and employee leasing from the perspective of employment law. This analysis was motivated by decisions by the Bundesarbeitsgericht (German Federal Labour Court) on aircraft leasing including the provision of aircraft personnel (wet lease). The Arbeitnehmerüberlassungsgesetz (Germany’s law on labour leasing) and the relevant provisions in European Union law are defined and discussed. Until now, there has been no academic analysis of this issue on this broad scale. Based on the results, a new concept is presented, which is intended to provide a basis for the assessment of this contractual constellation. On the example of wet lease contracts, the new assessment method is applied and discussed.
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