Encapsulation of Porphyrinic Photosensitizers into Polymers monitored by NMR Spectroscopy

Vermathen, Martina; Gjuroski, Ilche; Furrer, Julien (5 July 2016). Encapsulation of Porphyrinic Photosensitizers into Polymers monitored by NMR Spectroscopy (Unpublished). In: International Conference of Porphyrins and Phthalocyanines ICPP-9. Nanjing, China. 03.-08.07.2016.

Owing to several favorable properties such as phototoxicity combined with tumor accumulation and low dark toxicity, porphyrinic compounds have been playing an important role as photosensitizers in photodynamic therapy (PDT) for a long time. However, most porphyrinic photosensitizers exhibit low solubility in biological media due to their intrinsic tendency to aggregate in aqueous solutions thereby decreasing PDT efficiency. Formation of porphyrin-nanoparticles or porphyrin-polymer systems represents an elegant way to cope with this problem. Some porphyrin-carrier systems such as Photolon®, which is a polyvinylpyrrolidone (PVP) complex with chlorin e6 (Ce6), have already gained approval for medical application in PDT. [1, 2] Recently, we have characterized a series of naturally derived porphyrin and chlorin e6 derivatives by NMR spectroscopy with respect to their propensity to form aggregates, their aggregate structures, as well as their interactions with membrane models. [3] The results showed that the porphyrin and Ce6 compounds formed different aggregate structures due to their specific substitution patterns. Moreover, small structural modifications can have a large impact on the aggregation behavior and thus solubility of the compound. Therefore, the suitability of a carrier system needs to be adopted and optimized according to the specific properties of its guest compounds. To this respect, NMR spectroscopy has proved a powerful method for monitoring the disaggregation process and the interactions between host and guest compounds on a submolecular level as we have recently shown for Ce6-derivatives. [4]

The aim of the present study was to characterize and compare the disaggregation capability and loading capacity of different polymers, such as PVP and the triblock copolymer Kolliphor P188 (KP188) for selected porphyrin compounds and chlorin amino acid conjugates in biological media using NMR spectroscopy as the main technique. The analysis of the 1H-NMR chemical shift and line width changes allowed us to monitor and characterize in detail the disaggregation process in the presence of both PVP and KP188 polymers. Furthermore, intermolecular interactions between the polymers and the porphyrin compounds could be identified and characterized using 2D 1H-NOESY, T1 and T2 relaxation time measurements and 2D 1H-diffusion ordered spectroscopy (DOSY) experiments. The preferential binding sites of the polymers to the different porphyrins indicate that the formation of the complexes is mainly governed by hydrophobic interactions between the porphyrin and the polymers. In addition, the results suggest that PVP forms rather stable complexes with the porphyrins, while a dynamic equilibrium between free and bound porphyrins exists using KP188. This may have a considerable impact on the pharmacokinetic properties of the corresponding delivery systems. Further studies are currently in progress to investigate the cell metabolic response to the different delivery systems applying HR-MAS NMR spectroscopy.

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