615 Pharmakologie, Therapeutik
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Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes at both cellular and molecular levels. To advance our understanding of drug carrier uptake mechanisms, we employed fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), leveraging the unique benefits of two-photon (2P) excitation. Our approach utilized giant unilamellar vesicles (GUVs) as a simplified model system for cell membranes, labelled with the amphiphilic fluorescent dye 3,3′-dioctadecyloxa-carbocyanine (DiOC18(3)). Additionally, large unilamellar vesicles (LUVs) functioned as a drug carrier system, incorporating the spectrally distinct fluorescent sulforhodamine 101 (SRh101) as a surrogate drug. The investigation emphasized the diverse interactions between GUVs and LUVs based on the charged lipids employed. We examined the exchange kinetics and structural alterations of liposome carriers during the uptake process. Our study underscores the significance of employing 2P excitation in conjunction with FLIM and FCS. This powerful combination offers a valuable methodological approach for studying liposome interactions, positioning them as an exceptionally versatile model system with a distinct technical advantage.
The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology–Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.
Nowadays pharmaceutical analysis and industry could not be imagined without using chromatographic methods like the High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC). Therefore, the field of chromatography is already firmly anchored in the three important, regional pharmacopeias: EP, USP and JP. Deficits of specifications within these pharmacopoeias relating to the detector parameters sampling rate and signal filtration are the major motivation of this thesis. Furthermore investigations on the data acquisition and processing within the detectors and software products dealing with collected data were done. Several concepts like double entry method, smoothing optimization and signal filtration based on persistence have been developed and are used as tools to examine the data integrity of commercial Chromatography Data System (CDS), improve the signal-to-noise ratio of small peaks to lower the LOD and LOQ by efficient denoising, and determine the suitable filter parameters and sampling rates an user can apply on his system to accelerate the method development and validation. All developments have been tested on simulated and real chromatograms and have shown that they are suitable for their specific purposes. In the end optimizations in the concepts still exist but some new aspects in the long-term investigated field of chromatography have been discovered.