title: Biphasic release of gentamicin from chitosan/fucoidan nanoparticles for pulmonary delivery.
abstract: 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 10h, followed by a sustained release of up to 72h, 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 (0.5mg/kg), the intratracheal administration of GM-loaded CS/F NP (0.27mg/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.
authors.affiliation: Department of Food Science, College of Life Science, National Taiwan Ocean University, Keelung 20224, Taiwan. Electronic address: ychuang@mail.ntou.edu.tw.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Food Science, College of Life Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
authors.forename: Rou-Ying
authors.initials: RY
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Jiun-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan; School of Dentistry, National Defense Medical Center, Taipei 11490, Taiwan. Electronic address: jkchen@nhri.org.tw.
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005839:Gentamicins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005839:Gentamicins; D011134:Polysaccharides; D048271:Chitosan; C007789:fucoidan
keywords: Chitosan; Fucoidan; Gentamicin; Nanoparticle; Pulmonary delivery