International Journal of Pharmaceutics, 30 December 2015, Vol.496(2), pp.942-952
The study on cholangiocellular cell lines was conducted with mTHPP-loaded nanoparticles with different polymers as matrices. Nanoparticles were characterized and the effect of the carrier system was examined in vitro. Comparison of free substance, embedded substance and different materials revealed severe differences for cellular uptake and in vitro activity after activation by illumination. The photodynamic therapy with porphyrin derivatives is an established approach to targeted tumor therapy, but is still afflicted with disadvantages of the physicochemical characteristics of the photosensitizer. To overcome drug-related restrictions in photodynamic therapy, three 5,10,15,20-tetrakis(m-hydroxyphenyl) porphyrin (mTHPP)-loaded nanoparticulate formulations based on poly(dl-lactide-co-glycolide) (PLGA), poly(d,l-lactide) (PLA), and Eudragit® E were prepared in a consistent diameter range and compared with free mTHPP in vitro. Formulation behavior was investigated in two different cholangiocellular cell lines, EGI-1 and TFK-1.High cytotoxicity was shown for all photosensitizer loaded nanoparticle (NP) formulations and free mTHPP, with EC50 values ranging from 0.2 to 1.3μM. PLA based NP were not as effective in all performed tests as other formulations. Nanoparticulate embedded mTHPP remained photodynamically active and resulted in caspase-3 activation even at low concentrations of 250nM. PLGA based NP exhibited highest caspase-3 activation.For all formulations an effective intracellular accumulation of mTHPP was observed, whereby for mTHPP-Eudragit® E-NP a 200-fold drug accumulation was shown.Polymer based nanoparticles were shown to be an effective and highly active transport vehicle for the photosensitizer mTHPP in vitro. Problems like low solubility of free drug can be circumvented by successful embedding into nanoparticulate carrier systems, maintaining therapeutic effects of the photosensitizer.
Drug Delivery System ; Photodynamic Therapy ; Cholangiocarcinoma ; Nanoparticle ; Cytotoxicity ; Polymer Influence
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