Abstract
Background: Final elimination of some intracellular bacterial agents, such as Brucella, is often a complex issue and impossible to achieve, primarily due to the presence and survival of the bacteria within phagocytic cells. By penetrating into the cell membrane, drug delivery nanosystems can reduce the number of intracellular bacteria. The aim of this study was to assess the efficacy of chitosan nanoparticles on the delivery of gentamicin into Brucella infected J774A.1 murine cells in vitro. Materials and Methods: Chitosan nanoparticles (NPs) were synthesized using ionic gelation technique. The shape, size and charge of NPs, loading rate and release of the drug were investigated. Finally, the effects of gentamicin-loaded chitosan NPs (Gen-Cs) and free gentamicin on J774A.1 murine cells infected with these bacteria were examined. Results: The mean size and charge of NPs were computed as 100 nm and +28mV, respectively. The loading capacity of NPs was 22%. About 70% of the drug was released from NPs during the first 8 hours. Antimicrobial activity of the two formulations showed that MIC (minimum inhibitory concentration) of the Gen-Cs and free drug was 3.1 and 6.25 µg, respectively. The minimum bactericidal concentration of the NPs-loaded drug and free drug was 6.25 and 12.5 µg, respectively. Cell culture analysis revealed that there was a significant reduction in the load of the intercellular bacteria in J774A.1 murine cells in both formulations. Conclusion: Our results showed the Gen-Cs have a proper potential for optimal treatment of intracellular bacterial agents.
Highlights
Brucellosis is a prevalent zoonotic disease caused by the genus Brucella melitensis
It has been reported that the administration of doxycycline antibiotic in combination with streptomycin or gentamicin is efficacious in combating the disease [5]
Investigation of drug release from chitosan NPs Study of the drug release profile showed that a relatively burst release occurred during the initial 8 hours, such that about 70% of the drug was released during this time
Summary
Brucellosis is a prevalent zoonotic disease caused by the genus Brucella melitensis. More than 500,000 people are annually infect- GMJChitosan Nanoparticles Improve the Therapeutic Effect of Gentamicin on BrucellaOrganization (WHO) recommends the administration of two antibiotics, including doxycycline and rifampin for 6 months for the treatment of the disease [3, 4]. The high water solubility of gentamicin reduces its penetration into the cells and, the treatment of intracellular bacterial infections using this antibiotic poses a serious challenge [9,10,11] These problems may be solved employing drug delivery systems and such diseases can be cured more efficiently than it was previously [12,13,14,15]. Nanotechnology has created hope and opportunity for the treatment of intracellular infections using nanoparticles (NPs) as drug carriers as well as surmount the above-mentioned problems or, at least, enhance and optimize therapeutic effects of drugs when compared to the free ones [16, 17] These systems can lead to improvement in therapies, reduce the accumulation of drug inside the cell, as well as reduce the required doses of drug and the number of times of administration [18, 19]. Conclusion: Our results showed the Gen-Cs have a proper potential for optimal treatment of intracellular bacterial agents. [GMJ.2019;8:e1296] DOI:10.31661/gmj.v8i0.1296
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