藻酸钠-两性霉素 B 缀合物的合成及抗真菌活性评价。
Synthesis and evaluation of anti-fungal activities of sodium alginate-amphotericin B conjugates.
机构信息
Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyothi Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India.
Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyothi Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India.
出版信息
Int J Biol Macromol. 2018 Mar;108:1101-1109. doi: 10.1016/j.ijbiomac.2017.11.030. Epub 2017 Nov 7.
Sodium alginate (SA) was oxidized using periodate and amphotericin B (AmB) was conjugated via imine and amine linkages to the oxidized alginate. Oxidization drastically reduced the molecular weight (MW) of the alginate. The conjugates were highly water-soluble to the extent of 1000mg/mL making them useful for therapeutic applications. SA-AmB conjugates derived from 20 and 50% oxidized alginate were non-toxic to HEK 293T and RAW 264.7 cell line at 100μg/mL and was also non-hemolytic to human blood at 100μg/mL. In vitro release of AmB into phosphate buffer from the imine conjugates was negligible with less than 0.2% of the drug released in 48h. Capping of residual aldehyde handles using 2-ethanolamine or glycine resulted in increased release of the drug in vitro. Injectable gels of gelatin crosslinked with oxidized alginate incorporating the SA-AmB conjugates as well as AmB were also fabricated and drug release was examined. In vitro release from the gel discs showed that AmB was released to the extent of 15-20% in 2days. The SA-AmB conjugates showed potent anti-fungal activity against C. albicans, C. neoformans and C. parapsilosis. The injectable gels seem to have potential for prolonged release of AmB when implanted.
海藻酸钠(SA)用过碘酸盐氧化,两性霉素 B(AmB)通过亚胺和胺键连接到氧化的海藻酸钠上。氧化大大降低了海藻酸钠的分子量(MW)。这些缀合物具有极高的水溶性,可达 1000mg/mL,使其适用于治疗应用。 由 20%和 50%氧化海藻酸钠衍生的 SA-AmB 缀合物在 100μg/mL 时对 HEK 293T 和 RAW 264.7 细胞系无毒性,在 100μg/mL 时对人血也无溶血作用。亚胺缀合物在磷酸盐缓冲液中向 AmB 的体外释放可以忽略不计,48 小时内释放的药物不到 0.2%。使用 2-乙醇胺或甘氨酸封闭残留的醛基可以增加体外药物的释放。还制备了用氧化海藻酸钠交联的明胶的可注射凝胶,其中包含 SA-AmB 缀合物和 AmB,并检查了药物释放情况。凝胶盘的体外释放表明,AmB 在 2 天内释放了 15-20%。SA-AmB 缀合物对白色念珠菌、新生隐球菌和近平滑念珠菌表现出强烈的抗真菌活性。当植入时,可注射凝胶似乎具有延长 AmB 释放的潜力。