Abstract
This work describes the development of a gastroresistant antimicrobial formulation composed of two carriers, pectin and liposomes, intended to improve the efficiency of norfloxacin (NOR) against multi-resistant bacterial strains. The formulations showed physicochemical stability for 180 days (4 °C) in terms of size, polydispersity, and zeta potential of the vesicles, prolonging the in vitro release of NOR for 11 h. The hybrid nanocarriers improved the in vitro antimicrobial activity against different multidrug-resistant bacterial strains, such as Salmonella sp., Pseudomonas aeruginosa, E. coli and Campylobacter jejuni, in comparison to commercial NOR and liposomal suspensions. The in vivo toxicity assay in chicken embryos revealed that the hybrid systems were not toxic in any of the different parameters analyzed, a result also corroborated by the analyses of biochemical biomarkers of the chicken-embryos liver function.
Highlights
Antibiotics are among the most important class of drugs employed to minimize mortality caused by bacterial infections, preventing complications in medical and veterinary invasive interventions [1]
Novel therapies based on nanostructured drug delivery systems have been proposed, in order to improve the antimicrobial activity of traditional antibiotics, without compromising its safety
The antimicrobial activity of the hybrid formulations was determined against Salmonella Heildelberg, Salmonella Typhimuirium, Campylobacter jejuni, Pseudomonas aeruginosa and Avian Pathogenic Escherichia coli (APEC) multi-resistant strains, and the safety of the hybrid formulations was confirmed through the in vivo embryo chicken-test model
Summary
Antibiotics are among the most important class of drugs employed to minimize mortality caused by bacterial infections, preventing complications in medical and veterinary invasive interventions [1]. Organic–organic nanostructured delivery systems are hybrid pharmaceutical forms composed of at least two different organic matrices: protein–polymer, protein–lipid, polymer–polymer or lipid–polymer [10] This strategy combines the advantage of each excipient in a single system, providing specialized nanodevices for the specific interaction with the biological barrier of interest [11]. Pectin (PCT, Figure S2) is a biocompatible anionic heterosaccharide present in the cell wall of citrus fruits It has been widely described as a biopolymer matrix for drug-delivery systems [15,16] due to its resistance to low pH medium and the ability to interact with mucin, the major glycoprotein of mucous tissues. Nanohybrid formulations based on liposomes and PCT were investigated, in order to improve the antimicrobial activity of NOR (0.2% w/v) against multi-resistant bacteria and to protect the gastrointestinal tract after oral administration. The antimicrobial activity of the hybrid formulations was determined against Salmonella Heildelberg, Salmonella Typhimuirium, Campylobacter jejuni, Pseudomonas aeruginosa and Avian Pathogenic Escherichia coli (APEC) multi-resistant strains, and the safety of the hybrid formulations was confirmed through the in vivo embryo chicken-test model
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