Novel biodegradable polyanhydrides based on betulin disuccinate and sebacic acid
for medical purpose

Polymers obtained from renewable raw materials are a valuable group of compounds that are used in many industries, including the pharmaceutical industry. With the growing interest in biopolymers, there is a need to find new natural monomers that can replace petroleum-based raw materials. One of such natural compounds is betulin, a pentacyclic triterpene, that occurs in nature, e.g. in the outer layer of birch bark. Both betulin and its derivatives e.g. betulin disuccinate, exhibit a broad spectrum of biological activity, including anti-cancer activity, while being non-toxic to normal cells. The aim of this study was to obtain a new, biodegradable betulin-based polyanhydrides exhibiting anti-cancer activity. Polyanhydrides were obtained by melt polycondensation of betulin disuccinate 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. Polymers were used for the preparation of microspheres using emulsion (O/W) solvent evaporation technique. Under physiological conditions copolymers undergo hydrolytic degradation to betulin disuccinate, whose biological activity is known and confirmed and to sebacic acid approved by FDA for use in drug delivery systems. Polyanhydrides were also tested for cytostatic activity against a wide range of cancer cell lines (HeLa, MCF-7, A-549, U-87MG, KB and HepG2), proving its efficiency in inhibiting the growth of selected cell lines.