Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, M. Strzody 9, 44-100 Gliwice, Poland.
Department of Organic Chemistry, Poznan University of Medical Science, Grunwaldzka 6, 60-780 Poznan, Poland.
Int J Mol Sci. 2021 Jan 22;22(3):1090. doi: 10.3390/ijms22031090.
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.
在本研究过程中,通过两步缩聚法制备了一系列基于桦木酸双琥珀酸酯和聚(乙二醇)二羧酸衍生物的新型可生物降解聚酸酐。这些共聚物可以用作药物传递系统中的载体,以微球的形式存在。桦木酸及其衍生物具有广泛的生物活性,包括细胞毒性活性,这使它们成为有前途的治疗剂候选物质。基于桦木酸的聚酸酐制备的微球在药物传递系统中的应用具有广阔的前景,包括吸入系统。所得共聚物在生理条件下水解时释放出活性物质-桦木酸双琥珀酸酯。使用聚(乙二醇)衍生物作为共聚单体可以提高所得到的化合物的溶解度和生物利用度。通过乳液溶剂蒸发法制备了粒径在 0.5-25 µm 范围内的微球,并对其理化和空气动力学性质进行了分析。微球的形态特征取决于聚酸酐结构中聚乙二醇(PEG)段的存在。颗粒的孔隙率取决于所用 PEG 的量和分子量,以及均质化速度。使用 18,000 rpm 的均质化速度,从含有 20%wt 的 PEG 600 的聚酸酐中获得了最具多孔性的颗粒。