Dubashynskaya Natallia V, Bokatyi Anton N, Trulioff Andrey S, Rubinstein Artem A, Kudryavtsev Igor V, Skorik Yury A
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, 199004 Saint Petersburg, Russia.
Institute of Experimental Medicine, Acad. Pavlov St. 12, 197376 Saint Petersburg, Russia.
Pharmaceutics. 2023 Sep 28;15(10):2396. doi: 10.3390/pharmaceutics15102396.
Improving the biopharmaceutical properties of glucocorticoids (increasing local bioavailability and reducing systemic toxicity) is an important challenge. The aim of this study was to develop a dexamethasone phosphate (DexP) delivery system based on hyaluronic acid (HA) and a water-soluble cationic chitosan derivative, diethylaminoethyl chitosan (DEAECS). The DexP delivery system was a polyelectrolyte complex (PEC) resulting from interpolymer interactions between the HA polyanion and the DEAECS polycation with simultaneous incorporation of zinc ions as a cross-linking agent into the complex. The developed PECs had a hydrodynamic diameter of 244 nm and a ζ-potential of +24.4 mV; the encapsulation efficiency and DexP content were 75.6% and 45.4 μg/mg, respectively. The designed DexP delivery systems were characterized by both excellent mucoadhesion and prolonged drug release (approximately 70% of DexP was released within 10 h). In vitro experiments showed that encapsulation of DexP in polysaccharide nanocarriers did not reduce its anti-inflammatory activity compared to free DexP.
改善糖皮质激素的生物制药特性（提高局部生物利用度并降低全身毒性）是一项重大挑战。本研究的目的是基于透明质酸（HA）和水溶性阳离子壳聚糖衍生物二乙氨基乙基壳聚糖（DEAECS）开发一种地塞米松磷酸酯（DexP）递送系统。DexP递送系统是一种聚电解质复合物（PEC），它由HA聚阴离子与DEAECS聚阳离子之间的聚合物间相互作用产生，同时将锌离子作为交联剂掺入该复合物中。所制备的PEC的流体动力学直径为244 nm，ζ电位为+24.4 mV；包封率和DexP含量分别为75.6%和45.4 μg/mg。所设计的DexP递送系统具有优异的粘膜粘附性和延长的药物释放特性（约70%的DexP在10小时内释放）。体外实验表明，与游离DexP相比，将DexP包封在多糖纳米载体中不会降低其抗炎活性。
