Multidrug Core–Shell Bead: A System for Bacterial Infection Treatment in Fish
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This study was developed to improve the durability and bioavailability of polymer matrix containing the antibacterial agent’s bacitracin (BAC), berberine (BER) and sodium nitroprusside (SNP), an ionotropic gelation method was successfully applied to prepare alginate/chitosan core–shell beads. The structure and properties of different core–shell beads were characterized by scanning electron microscopy (SEM), zeta potential, Fourier transform infrared spectroscopy (FTIR), thermal analysis (DSC), swelling tests, bioadhesive assay, release kinetic profile and antibacterial/antibacteriostatic activity in bacterial model. The morphology of beads was investigated by SEM, display relatively spherical shape and revealed rough surface was also observed the appearance of cracks probably caused by partial collapsing of the polymer network during drying. The diameter means particle size observed was around 1.04 ± 0.13 mm, the particles showed a neutral value, around + 0.305 mV. Using UV–Vis technique was observed a high entrapment efficiency of compounds BAC, BER and SNP (> 95%) in the alginate/chitosan core–shell beads. As demonstrated, there is increase in the swelling degree in pH 6.2. The drug release profile showed a pH-dependent release kinetics. At pH 5.0 the most suitable kinetic model is Higuchi, at pH 6.2 a zero-order model is observed, while at pH 7.4 the Korsmeyer–Peppas model present a good fit. The presence of compounds on beads was confirmed using FTIR analyses, and the results indicated that there is no interaction between drugs and vehicle used in the formulation. We can consider after DSC analysis that beads containing BAC, BER and SNP are thermally more stable than separate formulations having the characteristics required for application at room temperature. The release system produced has physical characteristics that allow the storage of the drugs for long periods of time maintaining their chemical and pharmacological properties unchanged. The percentage of adhesion displayed value of 66%, that indicates the improvement in adherence time on the absorbing surfaces to improves drug bioavailability and effectiveness of compounds. In this study is displayed the additive effect between BAC, BER and SNP shown the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections. These results indicate that the proposed strategy improves drug bioavailability and effectiveness of compounds in the treatment of fish.
KeywordsBacitracin Berberine Sodium nitroprusside Alginate/chitosan core–shell bead
The authors acknowledge the financial support from the University of Brasilia, the Coordination for the Improvement of Higher Educational Personnel (CAPES code 001), the Federal District Research Foundation (FAPDF), the Scientific and Technological Development Foundation (FINATEC), program PIQ and the National Council for Scientific and Technological Development (CNPq). A.J.G. and C.N.L. conceived and designed the research. O.A.B (PhD student) and C.C.L (undergraduate student) carried out the experiments, worked on the characterization analyses and helped to write the article. A.J.G was responsible for helping in the characterization tests and for guiding the analyses of physico-chemical data. C.N.L. performed SEM assays. A.J.G. interpreted the results, T.A.C. and H.S.M. helped to perform the biological tests. V.P.M was responsible for support in the antimicrobial assays. O.A.B performed fish antimicrobial assays. A.J.G. and C.N.L wrote the manuscript. The authors declare no competing financial interests.
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