The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts
The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts
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DOI：
10.1111/jphp.12680
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发表时间：
2017-02-01
影响因子：
3.3
通讯作者：
Groppo, Francisco Carlos
中科院分区：
文献类型：
--
作者：
Nunes Ferreira, Luiz Eduardo;Muniz, Bruno Vilela;Groppo, Francisco Carlos
目的改进局部麻醉药给药系统以提高其药理学性能。然而，未研究这些制剂的致炎潜力。本研究比较了罗哌卡因（ropivacaine，ropi）在普通的，脂质体（MLV）或2-羟丙基-β-环糊精（HP-CD）制剂对细胞活力，细胞凋亡和细胞因子（IL-1，TNF-α，IL-6和IL-10）的释放在体外的影响。通过XTT和LIVE/DEAD测定来测量细胞活力。细胞凋亡进行流式细胞术，细胞因子释放测定ELISA assay.Key findingsHuman永生化角质形成细胞的活力减少了ropi和两种药物输送系统。然而，没有一种制剂诱导细胞凋亡。结果显示HaCaT和HGF对IL-1、TNF-α、IL-6和IL-10的调节作用不同。Ropi-HP-CD增加两倍的IL-6释放的HGF与对照相比，而100 m ropi-MLV导致所有促炎细胞因子的释放增加的HGF.ConclusionThe损失细胞活力是不相关的细胞凋亡。与普通制剂相比，与HP-CD复合的Ropi显示出类似的细胞因子释放模式。因此，对于罗哌卡因药物递送，HP-CD形式是比MLV形式更好的药物载体。
ObjectivesModified drug delivery systems have been developed to improve pharmacological properties of local anaesthetics. However, the inflammatory potential of these formulations was not investigated. This study compared the in-vitro effects of ropivacaine (ropi) in plain, liposomal (MLV) or 2-hydroxypropyl--cyclodextrin (HP--CD) formulations on cell viability, apoptosis and cytokine (IL-1, TNF-, IL-6 and IL-10) release.MethodsHuman immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100m ropi concentrations. The cell viability was measured by XTT and LIVE/DEAD assay. Apoptosis was performed by flow cytometry, and cytokine release was measured by ELISA assay.Key findingsHuman immortalized keratinocyte viability was reduced by ropi and both drug delivery systems. However, none of the formulations induced apoptosis. Results showed a differential regulation of IL-1 TNF-, IL-6 and IL-10 by HaCaT and HGF. Ropi-HP--CD increased twofold the IL-6 release by HGF in comparison with the control, while 100m ropi-MLV led to an increased release of all pro-inflammatory cytokines by HGF.ConclusionThe loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP--CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP--CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.