Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria

Author:

Alves Danilo Antonini1,Machado Daisy1,Melo Adriana1ORCID,Pereira Rafaella Fabiana Carneiro1,Severino Patrícia23ORCID,Hollanda Luciana Maria de3,Araújo Daniele Ribeiro4,Lancellotti Marcelo15ORCID

Affiliation:

1. Laboratory of Biotechnology (LABIOTEC), Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil

2. Laboratory of Nanotechnology and Nanomedicine (LNMed), Institute of Technology and Research (ITP), Aracaju, SE, Brazil

3. Tiradentes University (UNIT), Aracaju, SE, Brazil

4. Center of Natural Sciences and Humanities, Federal University of ABC (UFABC), Santo André, SP, Brazil

5. Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil

Abstract

Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or intravenous administration. Chemically, levofloxacin is the levorotatory isomer (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent. Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial DNA. Levofloxacin hasin vitroactivity against a broad range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. However, formulation of combined poloxamers thermoregulated (as Pluronic® F127) and levofloxacin for use in multiresistant bacterial treatment were poorly described in the current literature. Thus, the aim of the present work is to characterize poloxamers for levofloxacin controlled release and their use in the treatment of multidrug bacterial resistance. Micelles were produced in colloidal dispersions, with a diameter between 5 and 100 nm, which form spontaneously from amphiphilic molecules under certain conditions as concentration and temperature. Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement of antimicrobial activity againstEscherichia coli,Pseudomonas aeruginosa, andKlebsiella pneumoniaewhen compared with only levofloxacin. Furthermore, all formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion, poloxamers combined with levofloxacin have shown promising results, better than alone, decreasing the minimal inhibitory concentration of the studied bacterial multiresistance strains. In the future, this new formulation will be used after being tested in animal models in patients with resistant bacterial strains.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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