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. 2021 Jan 22;22(3):1090.
doi: 10.3390/ijms22031090.

Bioactive Betulin and PEG Based Polyanhydrides for Use in Drug Delivery Systems

Daria Niewolik  1 , Barbara Bednarczyk-Cwynar  2 , Piotr Ruszkowski  3 , Tomasz R Sosnowski  4 , Katarzyna Jaszcz  1
Affiliations

Bioactive Betulin and PEG Based Polyanhydrides for Use in Drug Delivery Systems

Daria Niewolik et al. Int J Mol Sci. .

Abstract

In the course of this study, a series of novel, biodegradable polyanhydrides based on betulin disuccinate and dicarboxylic derivatives of poly(ethylene glycol) were prepared by two-step polycondensation. These copolymers can be used as carriers in drug delivery systems, in the form of microspheres. Betulin and its derivatives exhibit a broad spectrum of biological activity, including cytotoxic activity, which makes them promising substances for use as therapeutic agents. Microspheres that were prepared from betulin based polyanhydrides show promising properties for use in application in drug delivery systems, including inhalation systems. The obtained copolymers release the active substance-betulin disuccinate-as a result of hydrolysis under physiological conditions. The use of a poly(ethylene glycol) derivative as a co-monomer increases the solubility and bioavailability of the obtained compounds. Microspheres with diameters in the range of 0.5-25 µm were prepared by emulsion solvent evaporation method and their physicochemical and aerodynamic properties were analyzed. The morphological characteristics of the microspheres depended on the presence of poly(ethylene glycol) (PEG) segment within the structure of polyanhydrides. The porosity of the particles depended on the amount and molecular weight of the PEG used and also on the speed of homogenization. The most porous particles were obtained from polyanhydrides containing 20% wt. of PEG 600 by using a homogenization speed of 18,000 rpm.

Keywords: betulin; biodegradable microspheres; cytostatic activity; drug delivery systems; polyanhydrides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Reaction scheme of the synthesis of polyanhydrides based on disuccinate betulin (DBB) and dicarboxylic derivatives of PEG.
Figure 2
Figure 2
1H NMR and 13C NMR spectra of polyanhydrides based on betulin disuccinate and dicarboxylic derivatives of PEG. (a) 1H NMR spectrum; (b) 13C NMR spectrum.
Figure 3
Figure 3
Gel-permeation chromatography (GPC) chromatograms of polyDBB_PEG_250_60 (A) and polyDBB_PEG_600_60 (B).
Figure 4
Figure 4
Anhydride bonds loss and weight loss of copolymers based on PEG 250 (A,C) and PEG 600 (B,D) during hydrolytic degradation in phosphate buffer conducted at 37 °C (n = 3, error bars, standard deviation).
Figure 5
Figure 5
Anhydride bond loss of copolymers based on PEG 250 (A) and PEG 600 (B) in the air at 25 °C (n = 3, error bars, standard deviation).
Figure 6
Figure 6
Scanning electron microscope (SEM) images of polyDBB_PEG_250_20 microspheres obtained by using homogenization speed of 3000 rpm (A) and 18,000 rpm (B) and polyDBB_PEG_250_40 microspheres obtained by using homogenization speeds of 3000 rpm (C) and 18,000 rpm (D).
Figure 7
Figure 7
SEM images of polyDBB_PEG_600_20 microspheres obtained by using homogenization speed of 3000 rpm (A), 18,000 rpm (B) and 9000 rpm (C).
Figure 8
Figure 8
Volume size distribution of particle fraction in powder inhalers, polyDBB_PEG_600_20 microspheres, obtained by using homogenization speed of 9000 rpm (A) and 18,000 rpm (B).
See this image and copyright information in PMC

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