用于改善壳聚糖水凝胶中阿霉素释放及放射性标记稳定性的藻酸盐层
The Alginate Layer for Improving Doxorubicin Release and Radiolabeling Stability of Chitosan Hydrogels.
作者信息
Kwon Jeong Il, Lee Chang-Moon, Jeong Hwan-Seok, Oh Phil-Sun, Hwang Hyosook, Lim Seok Tae, Sohn Myung-Hee, Jeong Hwan-Jeong
机构信息
Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, Jeonbuk 500-757 Republic of Korea.
Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeonnam 500-757 Republic of Korea.
出版信息
Nucl Med Mol Imaging. 2015 Dec;49(4):312-317. doi: 10.1007/s13139-015-0337-1. Epub 2015 May 8.
PURPOSE
Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated.
METHODS
Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 °C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 °C for 12 days.
RESULTS
Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10 μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the released Dox for 12 days was decreased to 47.6 ± 1.4, 51.1 ± 1.4, and 57.5 ± 1.6 % for 0.25, 0.50, and 1.00 mg Dox used, respectively. The radiolabeling stability of DI-CSH in human serum was improved by alginate layer.
CONCLUSIONS
The formation of alginate layer on the surface of the DI-CSH is useful for improving the drug release behavior and radiolabeling stability.
目的
通过与阴离子分子发生离子相互作用形成的壳聚糖水凝胶（CSH）适合作为药物载体和组织工程支架。然而，浸入生物流体后由于快速溶胀，药物从CSH的初始突释限制了其作为药物递送载体的广泛应用。在本研究中，对负载阿霉素（Dox）和I-131标记的CSH（DI-CSH）表面进行藻酸盐分层。研究藻酸盐分层对药物释放行为和放射性标记稳定性的影响。
方法
使用螯合剂对壳聚糖进行化学修饰以用于I-131标记。在I-131标记并混合Dox后，使用静电纺丝系统将壳聚糖溶液滴入三聚磷酸钠（TPP）溶液中以制备球形微水凝胶。将DI-CSH浸入藻酸盐溶液中30分钟以在其表面形成交联层。通过傅里叶变换红外光谱（FT-IR）和zeta电位分析确认DI-CSH表面藻酸盐层的形成。为了研究藻酸盐层的作用，在37℃下于磷酸盐缓冲盐水（PBS，pH 7.4）中对水凝胶进行体外Dox释放研究12天。在不同实验条件（人血清、生理盐水和PBS）下于37℃对水凝胶的放射性标记稳定性进行12天的ITLC评估。
结果
在CSH表面形成藻酸盐交联层未改变球形形态和平均直径（150±10μm）。FT-IR光谱和zeta电位值表明藻酸盐层成功形成于DI-CSH表面。在体外Dox释放研究中，用于负载入水凝胶的Dox为0.25、0.50和1.00mg时，DI-CSH在12天内释放的Dox总量百分比分别为60.9±0.8%、67.3±1.4%和71.8±2.5%。另一方面，形成藻酸盐层后，使用的Dox为0.25、0.50和1.00mg时，12天内释放的Dox百分比分别降至47.6±1.4%、51.1±1.4%和57.5±1.6%。藻酸盐层提高了DI-CSH在人血清中的放射性标记稳定性。
结论
在DI-CSH表面形成藻酸盐层有助于改善药物释放行为和放射性标记稳定性。
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