The Journal of pharmacy and pharmacology · 2016
The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts.
СтатьяНазвание и аннотация: Перевод в очереди
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Ferreira Luiz Eduardo Nunes, Muniz Bruno Vilela, Burga-Sánchez Jonny, Volpato Maria Cristina, de Paula Eneida, Rosa Edvaldo Antonio Ribeiro, Groppo Francisco Carlos
Аннотация
OBJECTIVES: Modified 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-β-cyclodextrin (HP-β-CD) formulations on cell viability, apoptosis and cytokine (IL-1α, TNF-α, IL-6 and IL-10) release.
METHODS: Human immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100 μm 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 FINDINGS: Human 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-1α TNF-α, IL-6 and IL-10 by HaCaT and HGF. Ropi-HP-β-CD increased twofold the IL-6 release by HGF in comparison with the control, while 100 μm ropi-MLV led to an increased release of all pro-inflammatory cytokines by HGF.
CONCLUSION: The loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP-β-CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP-β-CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.
METHODS: Human immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100 μm 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 FINDINGS: Human 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-1α TNF-α, IL-6 and IL-10 by HaCaT and HGF. Ropi-HP-β-CD increased twofold the IL-6 release by HGF in comparison with the control, while 100 μm ropi-MLV led to an increased release of all pro-inflammatory cytokines by HGF.
CONCLUSION: The loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP-β-CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP-β-CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.