Pluronic® mixed micelles as efficient nanocarriers for benzoporphyrin derivatives applied to photodynamic therapy in cancer cells

• Synergistic interaction of Pluronic P123 and F127 provided stable mixed micelles.
• Benzoporphyrin derivatives, A- and B- ring regioisomers, were evaluated in Pluronic micelles.
• Pluronic mixed micelles encapsulates A- and B- regioisomers of benzoporphyrins at monomeric form.
• High photo-activity was observed against cancer cells upon red light irradiation.
• Costs reduction and photodynamic efficiency pointed out the investigated system as potential drug.

In this study we attempted to develop Pluronic micelles delivering the photodynamic therapy photosensitizers benzoporphyrin derivatives (BPD). The BPD A-ring (BPDMA or Verteporfin®, the active drug of FDA/USA approved Visudyne®), its regioisomer ring-B (BPDMB, not used in Visudyne® formulation due its poor solubility) and a BPDMA/BPDMB mixture (BPD-Mixt) were formulated in Pluronic P123 or F127 as well as P123/F127 mixed micelles at two different mass ratios. P123/F127 presented the lowest critical micelle concentration showing high stability due synergistic aggregation of P123 and F127. Mixed micelles allowed the encapsulation of BPD as monomers enhancing their photophysical properties and stability during time even under diluted conditions. High loading was attributed to the strong hydrophobic affinity of BPD for micelle core especially in the binary system due synergistic aggregation of P123 and F127 demonstrating the high potential of these micelles to encapsulate hydrophobic drugs. The in vitro assays showed a photo-activity of BPD-Mixt comparable to that of BPDMA against HeLa and A549 cancer cells under red light. The use of BPD-mixed formulations avoids the complex separation steps of these regioisomers and implies in cost reduction. The proposed system allies costs reduction and photodynamic efficiency, which stimulates further development on this nanosystem and may be of clinical interest for cancer PDT.

Figure optionsDownload as PowerPoint slide