Chakraborty Shreyasi, Kar Nabanita, Kumari Leena, De Asit, Bera Tanmoy
Laboratory of Nanomedicine, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
Int J Nanomedicine. 2017 Jul 7;12:4849-4868. doi: 10.2147/IJN.S132114. eCollection 2017.
Type I hypersensitivity is an allergic reaction characterized by the overactivity of the immune system provoked by normally harmless substances. Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of treatment for type I hypersensitivity. Even though these drugs have the anti-allergic effect, they can have several side effects in prolong use. Cedrol is the main bioactive compound of with anti-tumor, anti-oxidative, and platelet-activating factor inhibiting properties.
In this study, the preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid carriers (NLCs) were evaluated. NLCs were prepared using Compritol 888 ATO and triolein as lipid phase and vitamin E d-α-tocopherylpolyethyleneglycol 1000 succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers.
The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C) and 91.93 nm (NLC-C). The particle had negative zeta potential values of -31.9 mV (NLC-C) and -44.5 mV (NLC-C). Type I anaphylactoid reaction in the animal model is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast cell degranulation and histamine release from mast cells. Furthermore, compound 48/80-evoked Ca uptake into mast cells was reduced in a dose-dependent manner by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I anaphylactoid response in vivo in mice and compound 48/80-induced mast cell activation in vitro are greatly enhanced by the loading of cedrol into the NLCs. The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C was found to be 11.5-fold greater than both prednisolone and cromolyn sodium.
Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery of cedrol to protect anaphylactic reactions.
I型超敏反应是一种过敏反应，其特征是免疫系统对通常无害的物质产生过度反应。糖皮质激素、抗组胺药或肥大细胞稳定剂是治疗I型超敏反应的选择。尽管这些药物具有抗过敏作用，但长期使用可能会有多种副作用。雪松醇是[具体物质]的主要生物活性化合物，具有抗肿瘤、抗氧化和抑制血小板活化因子的特性。
在本研究中，评估了载雪松醇纳米结构脂质载体（NLCs）的制备及其抗过敏作用。使用Compritol 888 ATO和三油酸甘油酯作为脂质相，维生素E d-α-生育酚聚乙二醇1000琥珀酸酯、大豆卵磷脂和脱氧胆酸钠作为纳米颗粒稳定剂来制备NLCs。
雪松醇-NLCs（CR-NLCs）的平均直径为71.2 nm（NLC-C）和91.93 nm（NLC-C）。颗粒的zeta电位值为负，分别为-31.9 mV（NLC-C）和-44.5 mV（NLC-C）。雪松醇和雪松醇-NLC可显著减轻动物模型中的I型类过敏反应。雪松醇的这种体内活性表明，雪松醇可抑制化合物48/80诱导的腹膜肥大细胞脱颗粒以及肥大细胞释放组胺。此外，雪松醇和雪松醇-NLC以剂量依赖性方式减少了化合物48/80引起的肥大细胞对钙的摄取。研究证实，将雪松醇载入NLCs可大大增强其对小鼠体内I型类过敏反应的抑制作用以及对体外化合物48/80诱导的肥大细胞活化的抑制作用。以泼尼松龙和色甘酸钠作为阳性对照，通过选择性指数（SI）评估了雪松醇和CR-NLC的安全性。发现CR-NLC-C的SI比泼尼松龙和色甘酸钠都大11.5倍。
在过敏反应发作前24小时给予CR-NLC可预防类过敏反应。NLCs可能是口服递送雪松醇以保护过敏反应的一种有前景的载体。
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