摘要或動機

In photodynamic therapy (PDT), reactive oxygen species are generated within the cytoplasm to destroy cancer cells selectively. Using porphyrinic structures (PS) as photosensitizers holds promise for targeting cancer cells. However, direct incorporation of the porphyrins into cancer cells remains elusive. Hence, Dr. Martina Vermathen’s research introduced specific membranous phospholipid nanocarriers for topical porphyrin applications. However, since a sufficiently high enough concentration of PS in cancer cells has not yet been achieved, this study aimed to improve skin uptake of the nanocarriers. Two approaches were examined: (1) comparing polar and nonpolar porphyrins and (2) assessing the effect of a penetration enhancer, DMSO, through a neat and diluted application. The polarity of the porphyrins was first quantified with a log P test. The nanocarriers were assembled by incorporating two different PS compounds, either the mono- or tetra-4-carboxy substituted phenyl porphyrin. They were then characterized by 1D and 2D-NMR analysis. The porphyrin permeation was tested by Franz diffusion tests on pig ear skin. For the second approach, DMSO was added in the Franz diffusion test, either directly applied on the skin (“neat“) or diluted in the nanocarriers (“diluted”). The log P test for the mono- and the tetra-carboxyphenyl porphyrin resulted in values of 4.5 and -1.1, respectively. The more polar tetra-carboxyphenyl porphyrin exhibited 2.8 times better skin uptake compared to the mono-carboxyphenyl porphyrin. The neat DMSO application increased uptake by a factor of 5.5. The diluted DMSO application worsened skin uptake slightly. Analytical techniques revealed differences in porphyrin encapsulation: The mono-carboxyphenyl porphyrins were encapsulated in the centre, whereas tetra-carboxyphenyl porphyrins were localised around the nanocarriers. Results indicated potential instability of the nanocarriers. The more polar tetra-substituted porphyrins showed superior skin diffusion than the mono-substituted derivative. The neat DMSO application facilitated enhanced skin uptake by inducing membrane destabilization and pore formation but may have limited applicability. Further research is suggested to explore porphyrinic PS with alternative polar substitution patterns and tailored penetration enhancers for lipid-based delivery systems. Overall, the study underscores the importance of molecular properties of the PS system and demonstrates the potential of penetration enhancers in optimizing PDT for skin cancer treatment.