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脂质体利多卡因与2-羟丙基-β-环糊精利多卡因对人角质形成细胞和牙龈成纤维细胞活力及炎症反应的比较

Comparison of liposomal and 2-hydroxypropyl-β-cyclodextrin-lidocaine on cell viability and inflammatory response in human keratinocytes and gingival fibroblasts.

作者信息

Ferreira Luiz Eduardo Nunes, Muniz Bruno Vilela, Dos Santos Cleiton Pita, Volpato Maria Cristina, de Paula Eneida, Groppo Francisco Carlos

机构信息

Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.

出版信息

J Pharm Pharmacol. 2016 Jun;68(6):791-802. doi: 10.1111/jphp.12552. Epub 2016 Apr 7.

Abstract

OBJECTIVES

The aim of this study was to observe the effect multilamellar liposomes (MLV) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in the in-vitro effects of lidocaine in cell viability, pro-inflammatory cytokines and prostaglandin E2 release of both human keratinocytes (HaCaT) and gingival fibroblasts (HGF) cells.

METHODS

HaCaT and HGF cells were exposed to lidocaine 100-1 μm in plain, MLV and HP-β-CD formulations for 6 h or 24 h. The formulation effects in cell viability were measured by XTT assay and by fluorescent labelling. Cytokines (IL-8, IL-6 and TNF-α) and PGE2 release were quantified by ELISA.

KEY FINDINGS

MLV and HP-β-CD formulations did not affect the HaCaT viability, which was significantly decreased by plain lidocaine after 24 h of exposure. Both drug carriers increased all cytokines released by HGF after 24-h exposure, and none of the carriers was able to reduce the PGE2 release induced by lidocaine.

CONCLUSION

The effect of drug carrier in the lidocaine effects was dependent on the cell type, concentration and time of exposure. MLV and HP-β-CD showed benefits in improving cell viability; however, both of them showed a tendency to increase cytokine release when compared to the plain solution.

摘要

目的

本研究旨在观察多层脂质体(MLV)和2-羟丙基-β-环糊精(HP-β-CD)对利多卡因在体外对人角质形成细胞(HaCaT)和牙龈成纤维细胞(HGF)细胞活力、促炎细胞因子及前列腺素E2释放的影响。

方法

将HaCaT和HGF细胞分别暴露于浓度为100 - 1μm的普通利多卡因、MLV和HP-β-CD制剂中6小时或24小时。通过XTT法和荧光标记测量制剂对细胞活力的影响。通过酶联免疫吸附测定(ELISA)对细胞因子(IL-8、IL-6和TNF-α)及PGE2释放进行定量分析。

主要发现

MLV和HP-β-CD制剂不影响HaCaT细胞活力,但暴露24小时后普通利多卡因显著降低了其活力。两种药物载体在暴露24小时后均增加了HGF释放的所有细胞因子,且没有一种载体能够降低利多卡因诱导的PGE2释放。

结论

药物载体对利多卡因作用的影响取决于细胞类型、浓度和暴露时间。MLV和HP-β-CD在提高细胞活力方面显示出益处;然而,与普通溶液相比,它们都有增加细胞因子释放的趋势。

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