The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts

Author:

Ferreira Luiz Eduardo Nunes1ORCID,Muniz Bruno Vilela1,Burga-Sánchez Jonny1,Volpato Maria Cristina1,de Paula Eneida2,Rosa Edvaldo Antonio Ribeiro3,Groppo Francisco Carlos1

Affiliation:

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

2. Department of Biochemistry, Biology Institute, University of Campinas – UNICAMP – Campinas, São Paulo, Brazil

3. Xenobiotics Research Unit, Laboratory of Stomatology, Biological and Health Sciences Center, The Pontifical Catholic University of Paraná – Curitiba, Paraná, Brazil

Abstract

Abstract 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.

Funder

FAPESP

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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