Star- and comb-shaped betulin-based polyanhydrides with anticancer activity—synthesis and characterization

Betulin exhibits a broad spectrum of biological relevance, including anticancer activity. Due to this, betulin and its derivatives, e.g. betulin disuccinate (DBB), can be used as new potential therapeutic agents. The presence of two carboxyl groups in DBB allows for the preparation of polyanhydrides.

The aim of this work was to obtain betulin-based highly branched polyanhydrides with star- or comb-shaped architectures. Branched polymers offer significantly different physical properties from linear polymers and can provide several advantages for drug delivery applications.

In this study, we develop novel highly branched polyanhydrides with different DBB contents and different architectures through the two-step melt polycondensation of DBB and polycarboxylic derivatives of succinic acid oligomers (OSAGE-COOH and PSAGE-COOH). The content of DBB in the polymers ranged from 70 to 95 wt %. The use of OSAGE-COOH as a branching agent allowed us to obtain star-shaped polymers, while the use of PSAGE-COOH resulted in comb-like polymers. The protein-staining sulforhodamine B assay, developed by the National Cancer Institute for in vitro antitumor screening, was employed in this study for the determination of the cytotoxic activity of the polymers.

The physicochemical properties of the polymers varied depending on the content and structure of DBB. All the obtained polymers released DBB as a result of hydrolysis under physiological conditions and exhibited cytostatic activity toward cancer cell lines while being non-toxic to normal cells. The obtained results offer a promising area for further research into these copolymers' use in medicine.

Branched betulin-based polyanhydrides exhibit anti-cancer activity; thus, they can be used as a polymeric prodrug. Due to their biodegradability and non-toxicity, they are also ideal candidates for carriers of other biologically active substances.