Biphasic release of gentamicin from chitosan/fucoidan nanoparticles for pulmonary delivery

• Chitosan/fucoidan nanoparticles (CS/F NPs) are potential carriers for gentamicin (GM) delivery.
• The release of GM from CS/F NPs is biphasic, attaining a value of 99% release.
• The GM-loaded CS/F NPs exhibited more effective antibacterial activity than free GM.
• The CS/F NPs facilitated antibacterial capability before GM were completely released.
• By intratracheal administration, GM-loaded CS/F NP presented a superior AUC/MIC ratio.

Gentamicin (GM), one of the most commonly used aminoglycoside antibiotics, has been used for treating pneumonia; however, the applicability of GM is limited by its bioavailability and toxic side effects. This study used chitosan (CS)/fucoidan (F) nanoparticles (NPs) to develop a nanoformulation for pulmonary delivery of GM, presenting a biphasic release feature. The NPs exhibited a zero-order release of GM for the first 10 h, followed by a sustained release of up to 72 h, attaining a value of 99%. The GM-loaded CS/F NPs provide multiple antimicrobial capabilities against Klebsiella pneumoniae, including the CS and biphasic release of GM. Compared with the intravenous administration of free GM (0.5 mg/kg), the intratracheal administration of GM-loaded CS/F NP (0.27 mg/kg) presented a superior area under the concentration–time curve/minimum inhibitory concentration ratio, indicating the simultaneous improvement of antimicrobial efficacy and elimination of systemic toxicity. These results suggested that CS/F NPs are potential carriers in pulmonary delivery of GM for pneumonia treatment.