Department of Pharmaceutics, Novel Drug Delivery System Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran.
Pharm Dev Technol. 2021 Apr;26(4):412-421. doi: 10.1080/10837450.2021.1883059. Epub 2021 Feb 10.
In the current study erythropoietin (EPO) loaded trimethyl chitosan/tripolyphosphate nanoparticles-embedded in a thermosensitive hydrogel was prepared. The influence of the main experimental factors on the properties of EPO-loaded nanoparticles were evaluated using a two-factors central composite design and the optimized formulation was then freeze dried. Sodium dodecyl sulfate-page and circular dichroismspectroscopy were used to confirm the structural stability of EPO following encapsulation and freeze drying. Rheological properties, and the release rate of EPO from the hydrogel were examined. Mean particle size, zeta potential, and entrapment efficiency of the optimized EPO-loaded nanoparticles were confirmed 151.5 ± 16 nm, 11.5 ± 1.8 mV, and 78.5 ± 5.9%, respectively. The hydrogel containing nanoparticles existed as a solution at room temperature converted to a semisolid upon increasing the temperature to 35 ± 1.2 °C and demonstrated controlled release of EPO for more than 10 days. The stability of EPO in the hydrogel system was further investigated using in vivo biological activity assay and the result revealed relative potency of 0.85 as calibrated with standard EPO. Finally, a single injection of the EPO-loaded nanoparticles-embedded in the hydrogel administered to Sprague-Dawley rats resulted in elevated reticulocytes for about 20 days compared to control group received blank hydrogel.
在本研究中，制备了载红细胞生成素（EPO）的三甲基壳聚糖/三聚磷酸盐水凝胶纳米粒。采用两因素中心复合设计评价了主要实验因素对载 EPO 纳米粒性质的影响，并对优化的配方进行了冷冻干燥。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和圆二色光谱法用于证实 EPO 包封和冷冻干燥后的结构稳定性。考察了水凝胶的流变性能和 EPO 的释放率。优化的载 EPO 纳米粒的平均粒径、Zeta 电位和包封效率分别为 151.5±16nm、11.5±1.8mV 和 78.5±5.9%。含有纳米粒的水凝胶在室温下呈溶液状态，当温度升高到 35±1.2°C 时转变为半固体状态，并表现出 EPO 的控释作用超过 10 天。通过体内生物活性测定进一步研究了 EPO 在水凝胶系统中的稳定性，结果表明其相对效价为 0.85，与标准 EPO 标定。最后，单次注射载 EPO 的纳米粒水凝胶在 Sprague-Dawley 大鼠中，与空白水凝胶组相比，网织红细胞升高约 20 天。
