Delivery of Ulva rigida extract by bicontinuous cubic lipid nanoplatforms for potential photodynamic therapy against pancreatic cancer

Ulva rigida is a widely available marine algae representing a valuable biomass from which natural photosensitizers (chlorophylls) can be obtained in an environmentally friendly manner using a green microwave-assisted extraction technique. If properly loaded in biocompatible nanoformulations, such highly hydrophobic chlorophylls with photosensitizing activity may constitute effective drugs useful in photodynamic therapy (PDT) against extremely resistant pancreatic cancer cells. To permit adequate solubilization in water, prevent immune system activation, and improve pharmacokinetic properties, an extract from Ulva rigida biomass was encapsulated in two monoolein-based cubosome formulations differing for the dispersants used for their stabilization in water: Pluronic F108 (CUB) or a mixture of sorbitan monooleate and sodium taurocholate (TS-CUB). In both cases, high encapsulation efficiency was achieved. The formulations were investigated from a physicochemical point of view (SAXS, cryo-TEM, DLS, ELS), and the production of reactive oxygen species was evaluated. In addition, an extensive evaluation of biocompatibility and bioactivity was conducted on the human pancreatic cancer cell line BxPC-3. This assessment included an MTT cytotoxicity assay, cellular uptake analysis via flow cytometry, and cytoskeleton imaging both under dark conditions and post-irradiation to evaluate the effects of PDT. Unloaded nanoparticles were characterized by an inner bicontinuous cubic phase (Pn3m). However, after encapsulation of the Ulva rigida extract the presence of a sponge phase (L3) in the TS-CUB formulation was observed. Compared with CUB, TS-CUB loaded with the extract demonstrated enhanced photoactivity, superior biocompatibility, and more potent in vitro anticancer activity against pancreatic cancer through photodynamic therapy (PDT).