Properties and antitumor activity of combined polymeric nanoparticles based on gefitinib and a photosensitizer

Introduction: Gefitinib (GFT) is a moderately lipophilic small quinazoline molecule with proven efficacy in treating locally advanced or metastatic non-small cell lung cancer. Due to the broad activity of GFT and other tyrosine kinase inhibitors, researchers worldwide strive to create various nanoparticles based on these substances, including their combinations with other active molecules. This study investigated morphology, release, and cytotoxic activity of micellar form of combination particles with GFT and a phthalocyanine photosensitizer in various tumor models. Materials and Methods: The micellar model was obtained by mixing/emulsifying the aqueous and organic phases using a continuous flow of nitrogen gas, an aqueous solution of poloxamer 188 as the aqueous phase, and a chloroform solution of the active substances as the organic phase. Conventional analytical and biological methods were used to characterize the obtained micelles. The average particle size and polydispersity index of the samples were determined by dynamic light scattering and microscopy. Release from particles was determined in vitro by quantifying free GFT released through the dialysis insert. Cytotoxic activity was studied on the cell lines of lung cancer NCI-H640, glioblastoma A 172, melanoma A 375, and breast cancer SK-BR-3. Results and Discussion: The micelles with GFT, a photosensitizer, poloxamer 188, and polyvinylpyrrolidone were spherical and nanosized. 50% of the encapsulated GFT was released from the micellar model in a phosphate buffer medium within about 10.0 h. Testing of micelles on a panel of four tumor cell lines in the dose range of 0.1-20 μg/mL showed high cytotoxic activity of the studied model, especially for lung cancer and glioblastoma. Conclusion: The obtained data suggest a promising in-depth study of micellar nanoparticles of GFT with a photosensitizer, especially concerning lung cancer and glioblastoma.