Novel Biodegradable Polyanhydrides Based on Betulin Disuccinate and Sebacic Acid for Medical Purpose
The paper describes synthesis and the characterization of novel biodegradable betulin-based polyanhydrides, exhibiting anti-cancer activity. Polyanhydrides were obtained by a melt polycondensation of a disuccinate betulin (3,28-di-O-succinyl betulin) and sebacic acid with the use of acetic anhydride. Mentioned polyanhydrides were then thoroughly characterized by 1H NMR and 13C NMR, size exclusion chromatography, differential scanning calorimetry and FT-IR spectroscopy. The content of sebacic acid in obtained copolymers was from 20 to 80 wt%. The use of sebacic acid as a comonomer increases the crystallinity of polymers. Under physiological conditions copolymers undergo hydrolytic degradation to betulin disuccinate, whose biological activity is known and confirmed and to sebacic acid approved by the US Food and Drug Administration (FDA) for use in drug delivery systems. Polyanhydrides were also tested for cytostatic activity against a wide range of cancer cell lines (HeLa, A-549, U-87MG, KB and HepG2), proving its efficiency in inhibiting the growth of selected cell lines. Obtained polymers can be used as carriers in drug delivery system, in form of microspheres. Microspheres with diameter within the range of Dn = 15–30 µm were prepared by using emulsion (O/W) solvent evaporation method.