Exploring Micelles and Nanospheres as Delivery Systems for Phenothiazine Derivatives in Cancer Therapy

<b>Objectives</b>: Cancer remains one of the leading causes of death worldwide, and thus, there is a need for the development of innovative and more effective treatment strategies. The aim of the study was to evaluate two types of nanoparticles-nanospheres and micelles-obtained from PLA-based polymers to discover their potential for delivering four types of phenothiazine derivatives. <b>Methods</b>: The morphology, drug-loading properties, cytocompatibility, hemolytic properties and anticancer activity were analyzed. <b>Results</b>: The micelles exhibited significantly higher drug-loading properties, release process and cytotoxic activity against cancer cells compared to the nanospheres. The micelles containing 5-methyl-12<i>H</i>-quino[3,4-<i>b</i>][1,4]benzothiazinium chloride with an OH group as a substituent in the 10-position of the quinobenzothiazine ring showed the highest drug-loading content, the most efficient drug release, the lowest hemolytic activity and the most significant cytotoxic effect against HeLa cells. <b>Conclusions</b>: The conducted study enabled the development of a delivery system for the new anticancer compound and showed that the choice of drug carrier has a crucial effect on its cytotoxic potential against cancer cells.