Title:Effects of 2-Hydroxypropil-Β-Cyclodextrin-Lidocaine on Tumor Growth and Inflammatory Response
VOLUME: 17 ISSUE: 7
Author(s):Luiz Eduardo Nunes Ferreira*, Henrique Ballassini Abdalla, Jéssica Pereira da Costa, Juliana Souza de Freitas Domingues, Jonny Burga-Sánchez, Francisco Carlos Groppo and Maria Cristina Volpato
Affiliation:Laboratory of Inflammation and Immunology, Guarulhos University, Guarulhos, Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, Laboratory of Inflammation and Immunology, Guarulhos University, Guarulhos, Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba
Keywords:Lidocaine, 2-hydroxypropyl-β-cyclodextrin, antiproliferative, Walker 256 carcinoma, paw edema, inflammatory
response.
Abstract:
Background: Antiproliferative and cytotoxic effects of lidocaine have been reported in tumor
cells. However, the use of these drugs is restricted due to their short action with rapid dispersion
from the injected site. The complexation of local anesthetics in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) is able to improve pharmacological features.
Objective: This study evaluated the antitumor effects of lidocaine and the complex HP-β-CD-lidocaine
(HP-β-CD-lido).
Methods: In vitro, human adenocarcinoma (HeLa) and keratinocytes (HaCaT) were exposed to lidocaine
formulations and cell viability, proliferation and apoptosis induction were measured. In vivo,
Walker 256 carcinoma cells were subcutaneously injected into the plantar region of the rat right hind
paw. The animals were treated with a local application of 5% lidocaine or 5% HP-β-CD-lido. Doxorubicin
(3 mg/Kg/day, intraperitoneal) was used as a positive control. Edema sizes were measured daily
and the release of cytokines (TNF-α, IL-1α and CXCL-1) and prostaglandin E2 was evaluated. Histological
analysis was also performed.
Results: HaCaT IG50 values were 846 μM and 2253 μM for lido and HP-β-CD-lido, respectively. In
HeLa cells, the IG50 was 1765 μM for lido and 2044 μM for HP-β-CD-lido. Lidocaine formulations
significantly reduced the paw edema on day 6 after Walker 256 cells inoculation. However, there were
no differences in the release of inflammatory mediators in comparison to the control group.
Conclusion: Lidocaine formulations were able to reduce the edema in vivo, without affecting the tumor-
induced inflammatory response. The antiproliferative effects of lidocaine formulations may have
contributed to tumor reduction.
