Peimanfard Shohreh, Zarrabi Ali, Trotta Francesco, Matencio Adrián, Cecone Claudio, Caldera Fabrizio
Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73441, Iran.
Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125 Torino, Italy.
Pharmaceutics. 2022 May 15;14(5):1059. doi: 10.3390/pharmaceutics14051059.
This study aimed to design and fabricate novel hydroxypropyl-β-cyclodextrin-based hypercrosslinked polymers, called nanosponges, as carriers for anticancer hydrophobic agents and compare them with host-guest complexes of hydroxypropyl-β-cyclodextrin, a remarkable solubilizer, to investigate their application in improving the pharmaceutical properties of the flavonoid naringenin, a model hydrophobic nutraceutical with versatile anticancer effects. For this purpose, three new nanosponges, crosslinked with pyromellitic dianhydride, citric acid, and carbonyldiimidazole, were fabricated. The carbonate nanosponge synthesized by carbonyldiimidazole presented the highest naringenin loading capacity (≈19.42%) and exerted significantly higher antiproliferative effects against MCF-7 cancer cells compared to free naringenin. Additionally, this carbonate nanosponge formed a stable nanosuspension, providing several advantages over the naringenin/hydroxypropyl-β-cyclodextrin host-guest complex, including an increase of about 3.62-fold in the loading capacity percentage, sustained released pattern (versus the burst pattern of host-guest complex), and up to an 8.3-fold increase in antiproliferative effects against MCF-7 cancer cells. Both naringenin-loaded carriers were less toxic to L929 murine fibroblast normal cells than MCF-7 cancer cells. These findings suggest that hydroxypropyl-β-cyclodextrin-based carbonate nanosponges could be a good candidate as a drug delivery system with potential applications in cancer treatment.
本研究旨在设计并制备新型的基于羟丙基-β-环糊精的超交联聚合物，即纳米海绵，作为抗癌疏水药物的载体，并将其与出色的增溶剂羟丙基-β-环糊精的主客体复合物进行比较，以研究它们在改善黄酮类化合物柚皮素（一种具有多种抗癌作用的典型疏水营养保健品）药物性质方面的应用。为此，制备了三种分别与均苯四甲酸二酐、柠檬酸和羰基二咪唑交联的新型纳米海绵。由羰基二咪唑合成的碳酸酯纳米海绵表现出最高的柚皮素负载量（约19.42%），并且与游离柚皮素相比，对MCF-7癌细胞具有显著更高的抗增殖作用。此外，这种碳酸酯纳米海绵形成了稳定的纳米悬浮液，与柚皮素/羟丙基-β-环糊精主客体复合物相比具有多个优势，包括负载量百分比提高约3.62倍、缓释模式（相对于主客体复合物的突释模式）以及对MCF-7癌细胞的抗增殖作用提高多达8.3倍。两种负载柚皮素的载体对L929小鼠成纤维正常细胞的毒性均低于对MCF-7癌细胞的毒性。这些发现表明，基于羟丙基-β-环糊精的碳酸酯纳米海绵可能是一种良好的药物递送系统候选物，在癌症治疗中具有潜在应用。
