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Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model

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Abstract

The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.

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Acknowledgements

María Florencia Sanchez thanks for the CONICET fellowship. We thank Dr. Paul Hobson, native speaker, for revision of the manuscript.

Funding

This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, grant number PIP 2013-2015, 11220120100461), the Fondo para la Investigación Científica y Tecnológica (FonCyT, grant number PICT 0173), and the Universidad Nacional de Córdoba (SECYT-UNC, grant number 162/12).

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Authors and Affiliations

  1. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA)-CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina

    María Florencia Sanchez, Luis Ignacio Tártara, Rubén Hilario Manzo & María Eugenia Olivera

  2. Farmacia Central, Hospital Nacional de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

    Susana Andrea Breda

  3. Instituto de Investigaciones en Ciencias de la Salud (INICSA)-CONICET and Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

    Elio Andrés Soria

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  1. María Florencia Sanchez
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  2. Susana Andrea Breda
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  3. Elio Andrés Soria
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  4. Luis Ignacio Tártara
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Correspondence to María Eugenia Olivera.

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Sanchez, M.F., Breda, S.A., Soria, E.A. et al. Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model. Drug Deliv. and Transl. Res. 8, 1000–1013 (2018). https://doi.org/10.1007/s13346-018-0523-7

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