Self‐Assembled Verteporfin Nanoparticles for Photodynamic and Light‐Independent Therapy in Glioblastoma

Verteporfin (VP) has been used for photodynamic therapy (PDT) for over 20 years, and new applications have brought it back into the spotlight. VP is hydrophobic and requires lipid carriers for clinical delivery as Visudyne. A nanosuspension of VP, termed NanoVP, that requires no carriers is developed, permitting delivery of VP alone in an aqueous solution. NanoVP is produced by solvent-antisolvent precipitation, with dimethyl sulfoxide as the preferable solvent of several screened. The initial formulation has a hydrodynamic diameter of 104 ± 6.0 nm, concentration of 133 ± 10 μM, polydispersity index (Pdi) of 0.12 ± 0.01, and zeta potential of -22.0 ± 0.93 mV. Seeking a concentration >500 μM, a zeta potential <-10 mV, a diameter <64 nm, and a Pdi < 0.2, eight synthesis parameters are probed, identifying three that modified nanoparticle diameter and three that modified nanoparticle dispersity. The diameter is tuned fourfold from 49.0 ± 4.4 to 195 ± 7.1 nm, and the solution concentration is increased by 6.3-fold to 838 ± 45.0 μM. Finally, the bioavailability and anticancer capacity of NanoVP in glioblastoma are evaluated. In all, this provides a framework for the modification of amorphous nanoparticle properties and a new formulation for clinical use of VP.