Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.
Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms.
Department of Bioprocess Engineering and Biotechnology, Universidade Federal do Paraná, Curitiba, Brazil.
Lina M
LM
Blandón
Laboratorio de Nanobiomateriales, CINDEFI, Depto. de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET (CCT La Plata), 1900 La Plata, Argentina.
German A
GA
Islan
Laboratorio de Nanobiomateriales, CINDEFI, Depto. de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET (CCT La Plata), 1900 La Plata, Argentina.
Guillermo R
GR
Castro
Laboratório de Glicobiologia Estrutural de Carboidratos de Algas Marinhas (GLICAM), Department of Biochemistry and Molecular Biology, Universidade Federal do Paraná, Curitiba, Brazil.
Miguel D
MD
Noseda
Department of Bioprocess Engineering and Biotechnology, Universidade Federal do Paraná, Curitiba, Brazil.
Vanete
V
Thomaz-Soccol
Department of Bioprocess Engineering and Biotechnology, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address: soccol@ufpr.br.
Carlos R
CR
Soccol
D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008863:Microspheres; D011134:Polysaccharides / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
D000464:Alginates; D000900:Anti-Bacterial Agents; D006603:Hexuronic Acids; D011134:Polysaccharides; D002939:Ciprofloxacin; D020723:Glucuronic Acid; C050180:kefir grain polysaccharide
Alginate; Antimicrobial activity; Ciprofloxacin; Controlled release; Hybrid gel microspheres; Kefiran; Kefiran-ciprofloxacin complex