Multi-charged nanoemulsion for photodynamic treatment of glioblastoma cell line in 2D and 3D in vitro models

Abstract

Multi-charged nanoemulsions (NE) were designed to deliver Cannabidiol (CBD), Indocyanine green (ICG), and Protoporphyrin (PpIX) to treat glioblastoma (GBM) through Photodynamic Therapy (PDT). The phase-inversion temperature (PIT) method resulted in a highly stable NE that can be scaled easily, with a six-month shelf-life. We observed the quasi-spherical morphology of the nanoemulsions without any unencapsulated material and that 89% (± 5.5%) of the material was encapsulated. All physicochemical properties were within the expected range for a nanostructured drug delivery system, making these multi-charged nanoemulsions promising for further research and development. NE-PIC (NE-Protoporphyrin + Indocyanine + CBD) was easily internalized on GBM cells after three hours of incubation. Nanoemulsion (NE and NE-PIC) did not result in significant cytotoxicity, even for GBM or non-tumorigenic cell lines (NHF). Phototoxicity was significantly higher for the U87MG cell than the T98G cell when exposed to: visible (430 nm) and infrared (810 nm) laser light, with a difference of about 20%. From 50 mJ.cm−2, the viability of GBM cell lines decreases significantly, ranging from 65% to 85%. The NE-PIC was also effective for inhibiting cell proliferation into a 3D spheroidal GBM cell model, which is promising for mimicking the tumor cell environment. Irradiation at 810 nm was more effective in treating spheroid due to its deeper penetration in complex structures. NE-PIC has the potential as a drug delivery system for photoinactivation and photo diagnostic of GBM cell lines, taking advantage of the versatility of its active components.