Nano and microparticle drug delivery systems for the treatment of Brucella infections.

Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis, an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells . Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients.

Comparison of the effects of human fetal umbilical cord-derived hyaluronic acid and fibroblast-derived exosomes on wound healing in rats.

INTRODUCTION: Exosomes and hyaluronic acid influence tissue regeneration and may be used as an alternative to more conventional wound treatment methods. This study compared how well hyaluronic acid from the human umbilical cord and exosomes from fibroblast cells heal burn wounds in a preclinical model. METHODS: Ninety-six male Westar rats were used and allocated into four groups: The treatment group received 10% hyaluronic acid (HA); the treatment group received 300 l of exosome solution (EX); the treatment group received phenytoin (PC); the negative control group received no treatment (NC). The wound healing process was evaluated after 3, 6, 9, and 12 days. Histopathological analysis was done on the skin biopsy taken from the wounds. Re-epithelialization, inflammatory cells (PMNs), lymphocytes (LYMs), granulation tissue, collagen maturation (fibrosis), and eschar formation parameters were assessed for histopathological evaluation. On a scale from 0 to 4, each parameter received a score. RESULTS: Compared to the PC and NC groups, the median score for re-epithelialization was greater in the HA and EX groups (P < 0.05). At three days, PMN abundance distinguished the PC and NC groups from the HA and EX groups (P < 0.01). Compared to the PC and NC groups, the HA and EX groups had a lower median LYM score (P < 0.01). We found no statistical difference between the four groups for granulation tissue and fibrosis (P > 0.05). The EX group had a lower average score for eschar formation than the PC, NC, and HA groups (P < 0.01). The HA and EX groups demonstrated faster healing in the clinical and microscopic examinations than the NC and PC groups. CONCLUSION: The results showed that hyaluronic acid and exosomes improved wound healing. Also, the study demonstrated that hyaluronic acid has better effects in the re-epithelization. The exosome was more effective than HA in eschar formation. Both compounds were more influential in the PMNs and LYMs parameters than other groups. The combination of both compounds should be assessed further to achieve better therapeutic effects on wound healing.

Nanobodies, the potent agents to detect and treat the Coronavirus infections: A systematic review.

The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no effective treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19. However, the use of classical antibodies raises complex issues. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, cost-effective production, and good tissue permeability, causing VHH to be regarded as an antiviral therapeutics. However, the small size of nanobodies may lead to low antigen binding affinity and rapid renal clearance. In this systematic review, the application of nanobodies in the treatment of COVID-19 infection and other similar infections (MERS and SARS) was reviewed.

Gentamicin-Loaded Chitosan Nanoparticles Improve Its Therapeutic Effects on Brucella-Infected J774A.1 Murine Cells.

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.

Presenting a rapid method for detection of Bacillus cereus, Listeria monocytogenes and Campylobacter jejuni in food samples.

OBJECTIVES: Listeria monocytogens, Bacillus cereus and Campylobacter jejuni are three toxin producing bacteria over the world, especially in Iran, and it is essential to find a certain, rapid procedure to identify these microorganisms. In this research, these bacteria were simultaneously detected by multiplex PCR technique in foods. MATERIALS AND METHODS: The primary approval of bacterial strains was performed by biochemical tests. PCR primers were designed based on the nucleotide sequences of the NHEB/NHEC gene of B. cereus, the hly gene of L. monocytogenes and the C gene of C. jejuni. The specificity of Multiplex PCR method was determined using seven food poisoning bacteria including Salmonella typhi, Shigella dysentery, Yersinia pestis, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum and Vibrio cholerae. To confirm the reaction, DNA extraction was performed from 30 food samples (milk), and gene amplification was performed by PCR. The length of amplified fragments was 300 bp, 210 bp and 160 bp for NHEB/NHEC, hly and C genes, respectively. RESULTS: The detection limits of the PCR method were 5, 4 and 3 pg for L. monocytogenes, B. cereus and C. jejuni, respectively. Specifisity test showed that this reaction is spesific to these 3 bacteria. CONCLUSION: In this study, we introduced a new multiplex PCR method for simultsnus detection of L. monocytogens, B. cereus and C. jejuni. These results can be used for detection of other toxin producing bacteria in food.