Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97490 Saint-Denis de La Réunion, France.
Biomaterials, Drug Delivery and Nanotechnology Unit, Centre for Biomedical and Biomaterials Research (CBBR), University of Mauritius, MSIRI Building, Réduit, Mauritius.
Carbohydr Polym. 2019 Aug 1;217:35-45. doi: 10.1016/j.carbpol.2019.04.014. Epub 2019 Apr 5.
One of the most effective strategies to enhance the bioavailability and the therapeutic effect of hydrophobic drugs is the use of nanocarriers. We have used κ-carrageenan extracted from Kappaphycus alvarezii to produce oligocarrageenan via an enzymatic degradation process. Polycaprolactone (PCL) chains were grafted onto the oligocarrageenans using a protection/deprotection technique yielding polycaprolactone-grafted oligocarrageenan. The resulting amphiphilic copolymers formed spherical nanomicelles with a mean size of 187 ± 21 nm. Hydrophobic drugs such as curcumin were efficiently encapsulated in the micelles and released within 24-72 h in solution. The micelles were non-cytotoxic and facilitated the uptake of curcumin by endothelial EA-hy926 cells. They also increased the anti-inflammatory effect of curcumin in TNF-alpha-induced inflammation experiments. Finally, in vivo experiments supported a lack of toxicity in zebrafish and thus the potential use of polycaprolactone-grafted oligocarrageenan to improve the delivery of hydrophobic compounds to different organs, including liver, lung and brain as shown in mice.
提高疏水性药物生物利用度和治疗效果的最有效策略之一是使用纳米载体。我们使用从 Kappaphycus alvarezii 中提取的κ-卡拉胶，通过酶解过程生产低聚卡拉胶。然后使用保护/脱保护技术将聚己内酯（PCL）链接枝到低聚卡拉胶上，得到聚己内酯接枝低聚卡拉胶。所得的两亲性共聚物在溶液中形成平均粒径为 187±21nm 的球形胶束。疏水性药物如姜黄素被有效地包封在胶束中，并在 24-72 小时内释放。胶束无细胞毒性，并促进内皮 EA-hy926 细胞摄取姜黄素。它们还增加了姜黄素在 TNF-α诱导的炎症实验中的抗炎作用。最后，体内实验支持聚己内酯接枝低聚卡拉胶在斑马鱼中没有毒性，因此有可能将其用于改善疏水性化合物向包括肝脏、肺和脑在内的不同器官的递送，这在小鼠中得到了验证。
