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一种用于美洛昔康高级递送的新型肌肉注射脂质体的研发:在骨科疼痛模型中的制备、表征、药代动力学、药效学及疼痛评估

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

作者信息

Hanna Pierre A, Al-Abbadi Hatim A, Hashem Mohamed A, Mostafa Aziza E, Mahmoud Yasmina K, Ahmed Eman A, Hegab Ibrahim M, Helal Ibrahim E, Ahmed Mahmoud F

机构信息

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Faculty of Medicine, University Hospital, King Abdulaziz University, Jeddah 80212, Saudi Arabia.

出版信息

Int J Pharm X. 2024 Sep 14;8:100284. doi: 10.1016/j.ijpx.2024.100284. eCollection 2024 Dec.

DOI:10.1016/j.ijpx.2024.100284
PMID:39323733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11422154/
Abstract

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, release, release kinetics mathematical modeling, and an pain model in dogs undergoing orthopedic surgeries, followed by pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved controlled release pattern and an enhanced pharmacokinetic behavior as manifested by higher t and AUC and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

摘要

疼痛会引发多种生理和退行性并发症。本研究旨在将美洛昔康(MLX)制成脂质体,以提高其溶解度并实现美洛昔康的控释,从而克服其水溶性差和作用时间相对较短的问题。脂质体通过薄膜水化法制备,随后进行超声处理。制剂特性测试包括粒径、跨距、包封率、载药量、稳定性、差示扫描量热法(DSC)、傅里叶变换红外(FT-IR)光谱、形态、释放、释放动力学数学建模,以及在接受骨科手术的犬类中建立疼痛模型,随后与参比标准莫比替尔(Mobitil®)进行药代动力学、药效学和疼痛评估研究。脂质体美洛昔康的粒径约为100 nm,包封率为82%,载药量为4.62%。稳定性研究、DSC和FT-IR光谱表明脂质体高度稳定。与莫比替尔相比,该制剂显示出改善的控释模式和增强的药代动力学行为,表现为更高的t和AUC以及更低的Cl/F。药效学研究和疼痛量表表明,脂质体美洛昔康在控制术后疼痛方面比莫比替尔更好。总之,将美洛昔康包封于脂质体中可提高其溶解度、稳定性以及疼痛管理特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/5334b23f8753/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/f8bb25277645/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/59064cce17c0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/fc5605a72c82/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/ebfc8acc30c3/gr3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/c6a4f9994e68/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/065b9c5c657f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/e2475012db42/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e6/11422154/5334b23f8753/gr8.jpg

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