■口服药物是最常见和最方便的途径,提供良好的患者依从性,但药物溶解度限制口服应用。塞来昔布,一种不溶性药物,需要连续高剂量口服给药,这可能会增加心血管风险。由药物和脂质辅料制备的纳米结构脂质载体可以有效提高药物的生物利用度,减少药物剂量,降低不良反应的风险。
■在这项研究中,我们制备了透明质酸修饰的塞来昔布纳米结构脂质载体(HA-NLCs),以提高塞来昔布的生物利用度,减少或预防药物不良反应。同时,我们成功构建了一套符合FDA标准的生物样本测试方法来研究HA-NLCs在大鼠体内的药代动力学。
■药代动力学分析证实HA-NLCs显著增强药物吸收,导致AUC0-t比参考制剂(Celebrex®)高1.54倍。此外,与未修饰的纳米结构脂质载体(CXB-NLCs)相比,HA-NLCs可增加药物的保留时间并改善其体内半衰期。
■HA-NLC显著增加塞来昔布的生物利用度。添加透明质酸延长了药物的体内作用持续时间,并降低了与频繁口服塞来昔布相关的心血管不良反应的风险。
UNASSIGNED: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions.
UNASSIGNED: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats.
UNASSIGNED: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug\'s half-life in vivo.
UNASSIGNED: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug\'s in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.