Ferreira Maria Kueirislene Amâncio, Mendes Francisco Rogenio Silva, Marinho Emmanuel Silva, Lima de Albuquerque Roberto, Guedes Jesyka Macedo, Teixeira Izabell Maria Martins, Menezes Ramon Róseo Paula Pessoa Bezerra de, Caldeira Vinicius Patricio Santos, Santos Anne Gabriella Dias, Frederico Marisa Jádna Silva, Barreto Antônio César Honorato, Domingues Inês, Rodrigues Tigressa Helena Soares, Menezes Jane Eire Silva Alencar de, Santos Hélcio Silva Dos
Postgraduate Program in Natural Sciences, Ceará State University, Fortaleza 60714-903, Brazil.
Center for Exact Sciences and Technology, Vale do Acaraú University, Sobral 62040-370, Brazil.
Pharmaceutics. 2025 Jul 30;17(8):981. doi: 10.3390/pharmaceutics17080981.
: The incorporation of bioactive molecules into mesoporous carriers is a promising strategy to improve stability, solubility, and therapeutic efficacy. In this study, we report for the first time the encapsulation of the synthetic chalcone 4-Cl into KIT-6 mesoporous silica and evaluate its cytotoxicity, toxicological profile, and pharmacological activities (antinociceptive, anti-inflammatory, and anxiolytic) using an in vivo zebrafish (Danio rerio) model. : Zebrafish were orally dosed with 4-Cl, 4-Cl/KIT-6, or KIT-6 (4, 20, 40 mg/kg) and mortality was recorded for 96 h. For analgesia, zebrafish pretreated with 4-Cl, 4-Cl/KIT-6, KIT-6, or morphine received a tail stimulus (0.1% formalin). Locomotor activity (quadrant crossings) was monitored for 30 min to assess analgesia (neurogenic: 0-5 min; inflammatory: 15-30 min). For inflammation, abdominal edema and weight gain were assessed 4 h after intraperitoneal carrageenan (1.5%). Zebrafish ( = 6/group) received 4-Cl, 4-Cl/KIT-6, or KIT-6 (4, 20, 40 mg/kg, p.o.). Controls received ibuprofen (100 mg/kg, p.o.) or 3% DMSO. Weight was measured hourly for 4 h post-carrageenan (difference between baseline and hourly weights). : Physicochemical characterizations confirmed successful encapsulation without compromising the ordered structure of KIT-6, as evidenced by a significant reduction in surface area and pore volume, indicating efficient drug incorporation. In vivo assays demonstrated that the 4-Cl/KIT-6 formulation maintained the pharmacological activities of the free chalcone, reduced toxicity, and, notably, revealed a significant anxiolytic effect for the first time. : These findings highlight KIT-6 as a promising platform for chalcone delivery systems and provide a solid basis for future preclinical investigations.
将生物活性分子掺入介孔载体是提高稳定性、溶解度和治疗效果的一种有前景的策略。在本研究中，我们首次报道了将合成查尔酮4-Cl封装到KIT-6介孔二氧化硅中，并使用体内斑马鱼（Danio rerio）模型评估其细胞毒性、毒理学特征和药理活性（抗伤害感受、抗炎和抗焦虑）。斑马鱼经口给予4-Cl、4-Cl/KIT-6或KIT-6（4、20、40 mg/kg），记录96小时内的死亡率。为了评估镇痛效果，用4-Cl、4-Cl/KIT-6、KIT-6或吗啡预处理的斑马鱼接受尾部刺激（0.1%福尔马林）。监测运动活性（象限交叉次数）30分钟以评估镇痛效果（神经源性：0-5分钟；炎症性：15-30分钟）。为了评估炎症，在腹腔注射角叉菜胶（1.5%）4小时后评估腹部水肿和体重增加。斑马鱼（每组n = 6）接受4-Cl、4-Cl/KIT-6或KIT-6（4、20、40 mg/kg，口服）。对照组接受布洛芬（100 mg/kg，口服）或3%二甲基亚砜。在注射角叉菜胶后4小时内每小时测量体重（基线体重与每小时体重之间的差异）。物理化学表征证实成功封装，且未破坏KIT-6的有序结构，表面积和孔体积显著减少证明了这一点，表明药物有效掺入。体内试验表明，4-Cl/KIT-6制剂保持了游离查尔酮的药理活性，降低了毒性，并且首次显著显示出抗焦虑作用。这些发现突出了KIT-6作为查尔酮递送系统的一个有前景的平台，并为未来的临床前研究提供了坚实的基础。
