LAUSR

BACKGROUND Antiproliferative and cytotoxic effects of lidocaine has been reported in tumor cells. However, the use of these drugs is restricted due to their short action with rapid dispersion from injected site. The complexation of local anesthetics in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) are 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 plantar region of the rat right hind paw. The animals were treated with local application of 5% lidocaine or 5% HP-β-CD-lido. Doxorubicin (3 mg/Kg/day, intraperitoneal) was used as positive control. Edema sizes were measured daily and the release of cytokines (TNF-α, IL-1α and CXCL-1) and prostaglandin E2 were evaluated. Histological analysis was also performed. RESULTS HaCaT IG50 was 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 control group. CONCLUSION Lidocaine formulations were able to reduce the edema in vivo, without affect the tumor-induced inflammatory response. The antiproliferative effects of lidocaine formulations may have contributed to tumor reduction.