Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, P.R China.
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, P.R China.
Colloids Surf B Biointerfaces. 2019 Mar 1;175:569-575. doi: 10.1016/j.colsurfb.2018.11.083. Epub 2018 Nov 30.
Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH (e.g., its low mechanical property) and is associated with the enhancement of materials performance, which is useful in a variety of biomedical applications. In the present work, a hybrid hydrogel that combines dexamethasone sodium phosphate (Dexp) and a polysaccharide (alginate) was explored via a calcium ion coordination strategy. With the addition of Ca to an aqueous solution of Dexp/alginate, the Ca/Dexp/alginate hybrid hydrogel formed spontaneously. The formed Ca/Dexp/alginate hybrid hydrogels were thoroughly characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). An in vitro drug release study indicated that the formed Ca/Dexp/alginate hybrid hydrogel provided a slower drug release rate than did the Ca/Dexp hydrogel, and the drug release behaviour could be finely tailored by the change of Ca concentration. More importantly, the subcutaneous injection of the Ca/Dexp/alginate hybrid hydrogel significantly extended the in vivo retention of the hydrogel in situ compared to that of the Ca/Dexp hydrogel. The in vivo pharmacokinetic analysis indicated that the Ca/Dexp/alginate hybrid hydrogel could greatly extend drug release in vivo and significantly improve drug bioavailability compared to the Ca/Dexp hydrogel. As such, the formed Ca/Dexp/alginate hybrid hydrogel combined the greater resilience of an alginate network with the long in vivo duration of a low-molecular-weight hydrogel (Ca/Dexp hydrogel) and remarkably enhanced drug bioavailability, which might open an avenue for the design of self-assembling steroidal drug-polysaccharide hybrid hydrogels for drug delivery applications.
将低分子量水凝胶 (LMWH) 与高分子水凝胶结合可以克服 LMWH 的缺点（例如，机械性能低），并提高材料性能，这在各种生物医学应用中很有用。在本工作中，通过钙离子配位策略探索了将地塞米松磷酸钠 (Dexp) 和多糖（藻酸盐）结合在一起的杂化水凝胶。将 Ca 添加到 Dexp/藻酸盐的水溶液中，Ca/Dexp/藻酸盐杂化水凝胶会自发形成。通过扫描电子显微镜 (SEM)、傅里叶变换红外光谱 (FTIR) 和粉末 X 射线衍射 (XRD) 对形成的 Ca/Dexp/藻酸盐杂化水凝胶进行了彻底的表征。体外药物释放研究表明，形成的 Ca/Dexp/藻酸盐杂化水凝胶的药物释放速度比 Ca/Dexp 水凝胶慢，并且可以通过改变 Ca 浓度来精细调整药物释放行为。更重要的是，与 Ca/Dexp 水凝胶相比，Ca/Dexp/藻酸盐杂化水凝胶的皮下注射可显著延长原位水凝胶在体内的保留时间。体内药代动力学分析表明，与 Ca/Dexp 水凝胶相比，Ca/Dexp/藻酸盐杂化水凝胶可大大延长体内药物释放时间，显著提高药物生物利用度。因此，形成的 Ca/Dexp/藻酸盐杂化水凝胶将藻酸盐网络的更大弹性与低分子量水凝胶（Ca/Dexp 水凝胶）的长体内持续时间相结合，显著提高了药物的生物利用度，为设计用于药物输送应用的自组装甾体药物-多糖杂化水凝胶开辟了道路。
