Department of Chemical Sciences, SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Castletroy, Co. Limerick V94 T9PX, Ireland.
COOK Ireland Limited, O'Halloran Rd, Castletroy, Co. Limerick V94 N8X2, Ireland.
Mol Pharm. 2021 Oct 4;18(10):3777-3794. doi: 10.1021/acs.molpharmaceut.1c00279. Epub 2021 Sep 21.
Antihistamines are capable of blocking mediator responses in allergic reactions including allergic rhinitis and dermatological reactions. By incorporating various H receptor antagonists into a lipid cubic phase network, these active ingredients can be delivered locally over an extended period of time owing to the mucoadhesive nature of the system. Local delivery can avoid inducing unwanted side effects, often observed after systematic delivery. Lipid-based antihistamine delivery systems are shown here to exhibit prolonged release capabilities. In vitro drug dissolution studies investigated the extent and release rate of two model first-generation and two model second-generation H antagonist antihistamine drugs from two monoacyglycerol-derived lipid models. To optimize the formulation approach, the systems were characterized macroscopically and microscopically by small-angle X-ray scattering and polarized light to ascertain the mesophase accessed upon an incorporation of antihistamines of varying solubilities and size. The impact of encapsulating the antihistamine molecules on the degree of mucoadhesivity of the lipid cubic systems was investigated using multiparametric surface plasmon resonance. With the ultimate goal of developing therapies for the treatment of allergic reactions, the ability of the formulations to inhibit mediator release utilizing RBL-2H3 mast cells with the propensity to release histamine upon induction was explored, demonstrating no interference from the lipid excipient on the effectiveness of the antihistamine molecules.
抗组胺药能够阻断过敏反应中的介质反应，包括过敏性鼻炎和皮肤病反应。通过将各种 H 受体拮抗剂纳入脂质立方相网络中，由于该系统具有粘膜粘附性，这些活性成分可以在较长时间内局部递药。局部递药可以避免引起系统性递药后常观察到的不良反应。本文展示了基于脂质的抗组胺递药系统具有延长释放的能力。体外药物溶解研究考察了两种模型第一代和两种模型第二代 H1 拮抗剂抗组胺药物从两种单酰基甘油衍生的脂质模型中的释放程度和释放速率。为了优化配方方法，通过小角 X 射线散射和偏振光对系统进行了宏观和微观表征，以确定在不同溶解度和大小的抗组胺药物掺入时所获得的中间相。使用多参数表面等离子体共振研究了包封抗组胺分子对脂质立方系统粘膜粘附性的影响。作为开发治疗过敏反应疗法的最终目标，利用具有诱导释放组胺倾向的 RBL-2H3 肥大细胞探索了制剂抑制介质释放的能力，证明脂质赋形剂对抗组胺药物分子的有效性没有干扰。
