Macrophage-targeted (1EGI) doxycycline chitosan/alginate nanoengineering to alleviate <i>Brucella melitensis</i> biovar3 (RihA protein) relapse with effective bactericidal activity: <i>In silico</i> study

Brucellosis is a prevalent zoonotic infection, primarily in the developing world. Treatment regimens for brucellosis involve multiple medications, including doxycycline (DOX), which regulates the immune system and macrophage activity. Nevertheless, the treatment of Brucella infection is constrained by its presence within macrophages, which exhibit unique anti-immune mechanisms. The internal pathway for DOX against Brucella melitensis and its molecular docking is crucial for targeting macrophages, for enhancing efficacy, and decreasing the dose and time of treatment. Method: This research aimed to accurately predict the targeting efficiency of doxycycline-loaded chitosan alginate (DOX-N) nanoparticles to macrophages. Mannose-decorated chitosan–sodium alginate nanoparticles were chosen for this purpose. In silico analysis was performed to predict the targeting efficacy of the nanocarrier. Result: The study found that Nano DOX and macrophage mannose receptors exhibited binding interactions on their surfaces. The ligand DOX interacted with hydrogen bonds to the macrophage target receptor with a −7.5[Formula: see text]kcal/mol interaction and four hydrogen bonds on the mannose receptor of the macrophage. Similarly, sodium alginate exhibited a (−6.2[Formula: see text]kcal/mol) docking score, while conventional DOX was (−5.1[Formula: see text]kcal/mol). The computational study confirmed that DOX-N has the potential to be a promising lead molecule for regulating the incidence of brucellosis infections. The binding affinity and efficacy of DOX-N loaded on chitosan and sodium alginate were designed and assessed. Conclusion: The results indicated that Nano DOX had a strong affinity for the specific macrophage receptor and specific protein site in B. melitensis.