Fluorescein-containing amphiphilic copolymers as promising objects for biomedical research

Abstract

Background. Polymeric nanoparticles are increasingly used as drug carriers. They demonstrate a significant improvement in the therapeutic efficacy of drugs and are widely studied as components of drug transport and release systems. Unlike other types of nanoparticles, depending on the nature and properties, polymeric carriers can be designed to target specific organs, tissues, or cells and ultimately biodegrade with minimal systemic toxicity. The study aimed to investigate the in vitro cytotoxicity of drug delivery systems based on nanoparticles of fluorescein-containing amphiphilic copolymers, as well as to assess their ability to penetrate the cell and the possibility of controlling this process. Materials and Methods. Copolymers obtained on the basis of 2-(dodecanoylamino)pentanedioic acid and 2-(octadecanoylamino)pentanedioic acid, polyethylene ether­diols, and fluorescein were used for the study. The surface-active properties of the copolymers and the solubilization ability of their colloidal solutions were examined. The cytotoxicity of fluorescein-containing copolymers and the activity of cellular enzymes were studied on live spermatozoa obtained from bull ejaculates of 2–6 mL, with a sperm concentration of 0.6–1.5×109 cells/mL and an activity of 7.5–8.0 points. Results. Two groups of amphiphilic copolyesters, with molar weights of polyethy­lene etherdiols from 600 to 1500 and different content of fluorescein were studied. Their surface-active properties and ability to solubilize lipophilic substances – drug analogs – were determined. It was found that the obtained copolyester dispersions do not exhibit cytotoxicity. During direct contact with germ cells, copolymers can penetrate the cell membrane and decompose with the release of fluorescein. This allows us to track their location in the structures of germ cells. Conclusion. The relationship between the structure of amphiphilic fluorescein-containing copolyester and the degree of their effect on living objects in vitro has been established. The composition of copolymers that do not exhibit cytotoxicity and can be used as drug transporters has been determined. It has been shown that the synthesized copolymers can penetrate the membrane of germ cells and are decomposed during metabolic processes in sperm with the release of fluorescein.

Keywords

• amphiphilic copolyester
• fluorescein
• cytotoxicity
• enzyme activity