Background: Ticagrelor (TG), an antiplatelet drug is employed to treat patients with acute coronary syndrome, but its inadequate oral bioavailability due to poor solubility and low permeability restricts its effectiveness.
Purpose: This contemporary work was aimed to design a novel pH-sensitive nanocomposite hydrogel (NCH) formulation incorporating thiolated chitosan (TCH) based nanoparticles (NPs) of Ticagrelor (TG), to enhance its oral bioavailability for effectively inhibiting platelet aggregation.
Methods: NCHs were prepared by free radical polymerization technique, using variable concentrations of chitosan (CH) as biodegradable polymer, acrylic acid (AA) as a monomer, N,N-methylene bisacrylamide (MBAA) as cross-linker, and potassium persulphate (KPS) as initiator.
Results: The optimum hydrogel formulation was selected for fabricating NCHs, considering porosity, sol-gel fraction, swelling studies, drug loading capacity, and TG’s in vitro release as determining factors. Outcomes of the studies have shown that the extent of hydrogel swelling and drug release was comparatively greater at higher pH (7.4). Moreover, an amplifying trend was observed for drug loading and hydrogel swelling by increasing AA content, while it declined by increasing MBAA. The NCHs were evaluated by various physicochemical techniques and the selected formulation was subjected to in vivo bioavailability studies, confirming enhancement of bioavailability as indicated by prolonged half-life and multifold increase in area under the curve (AUC) as compared to pure TG.
Conclusion: The results suggest that NCHs demonstrated a pH-responsive, controlled behavior along with enhanced bioavailability. Thus NCHs can be effectively utilized as efficient delivery systems for oral delivery of TG to reduce the risk of myocardial infarction.



中文翻译：

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用于替格瑞洛受控递送的 pH 响应纳米复合水凝胶；体外和体内方法

背景：替格瑞洛（TG）是一种抗血小板药物，用于治疗急性冠脉综合征患者，但由于溶解度差和渗透性低，其口服生物利用度不足，限制了其有效性。
目的：这项当代工作旨在设计一种新型的 pH 敏感纳米复合水凝胶 (NCH) 制剂，其中包含基于硫醇化壳聚糖 (TCH) 的替格瑞洛 (TG) 纳米粒子 (NPs)，以提高其口服生物利用度，从而有效抑制血小板聚集。
方法：采用不同浓度的壳聚糖（CH）作为可生物降解聚合物，丙烯酸（AA）作为单体，N,N-亚甲基双丙烯酰胺（MBAA）作为交联剂和过硫酸钾，通过自由基聚合技术制备NCH。 KPS) 作为发起人。
结果：考虑孔隙率、溶胶-凝胶分数、溶胀研究、载药能力和 TG 的体外释放作为决定因素，选择了最佳水凝胶配方来制造 NCH。研究结果表明，水凝胶溶胀和药物释放的程度在较高的 pH 值（7.4）下相对较大。此外，随着 AA 含量的增加，载药量和水凝胶溶胀呈放大趋势，而随着 MBAA 含量的增加而下降。通过各种物理化学技术对 NCH 进行评估，并对所选制剂进行体内生物利用度研究，证实与纯 TG 相比，半衰期延长和曲线下面积 (AUC) 增加倍数表明其生物利用度增强。
结论：结果表明，NCHs 表现出对 pH 值敏感的受控行为以及增强的生物利用度。因此，NCHs 可以有效地用作 TG 口服递送的有效递送系统，以降低心肌梗塞的风险。