Revealing Changes in Celecoxib Nanostructured Lipid Carrier’s Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS

Yi Zhu,1,2,* Meiling Chen,3,* Chuangzan Yang,1,2 Geng Lu,1,2 Sa Huang,1,2 Meili Chen,3 Yufei Wang,4 Junfeng Ban1– 3 1Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, People’s Republic of China; 4Analytical and Testing Center of Guangzhou University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufei Wang; Junfeng Ban, Email yufei_wang@gzhu.edu.cn; banjunfeng@163.comPurpose: 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.Methods: 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.Results: 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.Conclusion: 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. Keywords: nanostructured lipid carriers, celecoxib, HPLC-MS/MS, pharmacokinetics