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

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-07-29 DOI:10.2147/dddt.s461969

Yi Zhu, Meiling Chen, Chuangzan Yang, Geng Lu, Sa Huang, Meili Chen, Yufei Wang, Junfeng Ban

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引用次数: 0

Abstract

Purpose: 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 AUC_0-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

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通过 HPLC-MS/MS 揭示以透明质酸为增强剂的塞来昔布纳米结构脂质载体生物利用度的变化

目的：口服给药是最常见、最方便的给药途径，患者依从性好，但药物溶解性限制了口服应用。塞来昔布是一种不溶性药物，需要连续大剂量口服给药，可能会增加心血管风险。利用药物和脂质辅料制备的纳米结构脂质载体可有效提高药物的生物利用度，减少药物用量，降低不良反应风险：本研究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，研究了HA-NLCs在大鼠体内的药代动力学：药代动力学分析证实，HA-NLCs 能显著促进药物吸收，其 AUC0-t 是参比制剂（Celebrex®）的 1.54 倍。此外，与未改性的纳米结构脂质载体（CXB-NLCs）相比，HA-NLCs能延长药物在体内的保留时间并改善药物的半衰期：结论：HA-NLCs能明显提高塞来昔布的生物利用度。结论：HA-NLCs能明显提高塞来昔布的生物利用度，透明质酸的加入延长了药物在体内的作用时间，降低了频繁口服塞来昔布引起心血管不良反应的风险。关键词：纳米结构脂质载体、塞来昔布、HPLC-MS/MS、药代动力学

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.