Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, Karnataka, India.
PLoS One. 2022 Apr 26;17(4):e0264518. doi: 10.1371/journal.pone.0264518. eCollection 2022.
Celecoxib (CLB) is a highly hydrophobic selective cyclo-oxygenase inhibitor with high plasma protein binding and undergoes extensive hepatic metabolism. CLB is highly effective in the treatment of osteo and rheumatoid arthritis as first line therapy but produces severe gastro-intestinal toxicities and cardiovascular side effects. In this research, stealth liposomes of CLB were developed with the intention to reduce the side effects and increase the accumulation of drug in the sites of inflammation. Stealth liposomes were prepared by thin film hydration technique using distearoylphosphatidylcholine and PE-PEG 2000 with variable amounts of cholesterol and characterized. The effects of various lipids such as hydrogenated soy phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoylphosphatidylcholine and cholesterol content on % drug encapsulation was investigated. The optimized stealth liposomes were characterized by FT-IR and DSC for possible drug excipients interaction. Pharmacokinetics, pharmacodynamics and biodistribution studies were carried out for the stealth liposomes. The results revealed that the stealth liposomes reduced the inflammation to the larger magnitude and have also sustained the magnitude when compared to free drug along with maximum analgesic response. Higher elimination half-life, AUC, MRT and lowered clearance rate denotes the extended bioavailability of the drug in blood. Biodistribution studies revealed that stealth liposomes extend the circulation time of liposomes in blood by decreasing opsonisation and be less concentrated in kidney, thereby reducing the toxicities to RES and renal organs and facilitate the drug accumulation in the area of inflammation. Our results indicated that CLB, without the requirement of modifications to enhance solubilisation, can be encapsulated and released from liposomal formulations. This new-fangled drug delivery approach may be used to circumvent the low bioavailability and toxic side effects of oral CLB formulations.
塞来昔布（CLB）是一种高度疏水性的选择性环氧化酶抑制剂，具有较高的血浆蛋白结合率，并经历广泛的肝代谢。CLB 在治疗骨关节炎和类风湿关节炎方面非常有效，作为一线治疗药物，但会产生严重的胃肠毒性和心血管副作用。在这项研究中，开发了 CLB 的隐形脂质体，旨在减少副作用并增加药物在炎症部位的积累。隐形脂质体通过薄膜水化技术制备，使用二硬脂酰基磷脂酰胆碱和 PE-PEG 2000，并用不同量的胆固醇进行特征化。研究了各种脂质，如氢化大豆磷脂酰胆碱、二棕榈酰磷脂酰胆碱、二硬脂酰基磷脂酰胆碱和胆固醇含量对药物包封率的影响。优化的隐形脂质体通过 FT-IR 和 DSC 进行特征化，以研究可能的药物赋形剂相互作用。进行了药代动力学、药效学和生物分布研究。结果表明，隐形脂质体可更大程度地减轻炎症，并与游离药物相比，可维持更大的炎症缓解程度，同时具有最大的镇痛反应。更高的消除半衰期、AUC、MRT 和降低的清除率表示药物在血液中的生物利用度延长。生物分布研究表明，隐形脂质体通过减少调理作用来延长脂质体在血液中的循环时间，并减少在肾脏中的积聚，从而降低对 RES 和肾脏器官的毒性，并促进药物在炎症部位的积累。我们的结果表明，CLB 无需进行增强溶解度的修饰即可被包裹并从脂质体制剂中释放。这种新颖的药物递送方法可用于避免口服 CLB 制剂的低生物利用度和毒副作用。
