Introduction: Microbial infections remain a major global health threat, with antibiotic resistance exacerbating the problem. Gentamicin, a broad-spectrum antibiotic, faces resistance chal-lenges. Nanotechnology, particularly dendrimers, offers a solution by enhancing drug delivery and efficacy. Materials and Methods: First- (G1) and second-generation (G2) PEG-citric acid dendrimers were synthesized, characterized via FT-IR and Zetasizer, and conjugated with gentamicin. Antimicrobial activity was assessed against Staphylococcus spp. and Pseudomonas aeruginosa using MIC and MBC assays. Results: The gentamicin-dendrimer conjugate showed a 16% drug loading efficiency and particle sizes of 70–184 nm. FT-IR confirmed successful conjugation. The conjugate exhibited 2–8 times greater antimicrobial efficacy than free gentamicin, particularly against S. aureus and P. aeruginosa. Discussion: Enhanced efficacy was attributed to improved solubility, electrostatic interactions, and bacterial membrane penetration. Dendrimer conjugation presents a promising strategy to combat re-sistance. Conclusion: Gentamicin-conjugated dendrimers significantly improve antibiotic performance, offer-ing a potential solution to antimicrobial resistance. Further toxicity and in vivo studies are warranted.
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