Dexamethasone-diclofenac loaded polylactide nanoparticles: Preparation, release and anti-inflammatory activity
Dexamethasone-diclofenac loaded polylactide nanoparticles: Preparation, release and anti-inflammatory activity
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DOI：
10.1016/j.ejps.2018.07.012
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发表时间：
2018-09-15
影响因子：
4.6
通讯作者：
Alhimony, Imad-Aldin
中科院分区：
文献类型：
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作者：
Assali, Mohyeddin;Shawahna, Ramzi;Alhimony, Imad-Aldin
炎症是组织对各种刺激和/或损伤的非特异性反应，这些刺激和/或损伤与引起疼痛、发烧和一般疾病感的各种介质的释放有关。通过服用非类固醇或类固醇抗炎药可以减少这种反应。这些抗炎药具有各种副作用。 However, the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with glucocorticoids provides a synergistic anti-inflammatory and pain relief with less side effects.在这项研究中，我们的目的是合成一种新型双药地塞米松-双氯芬酸，将其配制成聚丙交酯（PLA）纳米颗粒，以提高其溶解度并提供缓释系统。通过酯化反应合成双药，然后将其封装到 PLA 纳米颗粒中。在使用和不使用酯酶的情况下，体外研究了合成的双药的水解和 PLA 纳米颗粒的药物释放。在 BALB/c 小鼠中研究了抗炎活性。成功合成双药后，通过将其封装到PLA纳米颗粒中，提高了其水溶性，负载量为66%。体外释放显示双药的持续释放曲线长达 52 小时。酯酶水解表现出快速释放，1.5 小时后水解达到最大。此外，治疗6小时后，与母药相比，抗炎活性表现出协同作用，对TNF-α水平的抑制百分比更高。总之，所制备的纳米双药是一种新型疗法，具有缓释特性和优异的抗炎活性。
Inflammation is a nonspecific response of tissues to diverse stimuli and/or insults associated with the release of various mediators that induce pain, fever, and general sense of illness. Such responses can be reduced by the administration of non-steroidal or steroidal anti-inflammatory drugs. These anti-inflammatory drugs are associated with various side effect. However, the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with glucocorticoids provides a synergistic anti-inflammatory and pain relief with less side effects. In this study, we aimed to synthesize a novel twin-drug of Dexamethasone-Diclofenac formulated into polylactide (PLA) nanoparticles to improve their solubility and provide a sustained release system. The twin-drug was synthesized through an esterification reaction which was then encapsulated into PLA nanoparticles. The hydrolysis of the synthesized twin-drug and drug release from PLA nanoparticles were studied in vitro with and without esterase enzyme. The anti-inflammatory activity was studied in BALB/c mice. After the successful synthesis of the twin-drug, its water solubility was improved by its encapsulation into PLA nanoparticles with a loading capacity of 66%. The in vitro release showed a sustained release profile of the twin-drug up to 52 h. The esterase hydrolysis showed a rapid release with a maximum hydrolysis after 1.5 h. Moreover, the anti-inflammatory activity exhibited a synergistic effect with a higher percentage of inhibition for the TNF-alpha level in comparison to the parent drugs after 6 h treatment. In conclusion, the prepared nano twin-drug is a novel therapy that showed a sustained release profile with an excellent anti-inflammatory activity.