Novel Biodegradable Polyanhydrides Based on Betulin Disuccinate and Sebacic Acid for Medical Purpose

Daria Niewolik,Barbara Bednarczyk-Cwynar,Katarzyna Jaszcz,Piotr Ruszkowski

doi:10.3390/asec2020-07558

Daria Niewolik, Barbara Bednarczyk-Cwynar + Show 2 more

Open Access

https://doi.org/10.3390/asec2020-07558

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Abstract

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.

Highlights

Polymers obtained from renewable raw materials are a valuable group of compounds that are used in many industries, including the pharmaceutical ones
The aim of this work was the synthesis and characterization of polyanhydrides composed of betulin disuccinate and sebacic acid
Polyanhydrides were obtained by melt polycondensation of betulin disuccinate and sebacic acid with the use of acetic anhydride

Summary

Introduction

Polymers obtained from renewable raw materials are a valuable group of compounds that are used in many industries, including the pharmaceutical ones. Natural monomers used for polymerization include furans, terpenes and lactic acid [1]. Compared to polymers based on furan and lactic acid, much less attention is paid to the polymerization of terpenes. Terpenes are compounds widely occurring in nature, produced by a variety of plants and animals. They show a broad spectrum of biological activity [2]. A pentacyclic triterpene, 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 anticancer activity, while being non-toxic to normal cells [3].

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