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Current Drug Delivery

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

DOI: 10.2174/1567201817666200512101448

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Effects of 2-Hydroxypropil-Β-Cyclodextrin-Lidocaine on Tumor Growth and Inflammatory Response

Page: [588 - 598] Pages: 11

  • * (Excluding Mailing and Handling)

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.

Keywords: Lidocaine, 2-hydroxypropyl-β-cyclodextrin, antiproliferative, Walker 256 carcinoma, paw edema, inflammatory response.

Graphical Abstract

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