Dual tobramycin and docosahexaenoic acid loaded nanoemulsions combating Pseudomonas aeruginosa-induced pulmonary infection.

Autor: Sun Y; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Lu T; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Pan J; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., He H; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Xu M; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Chen Y; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Chen Y; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Fang P; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Ye X; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Li S; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China., Hu H; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China. Electronic address: lsshhy@mail.sysu.edu.cn., Yu S; School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China. Electronic address: yushh8@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2024 Oct; Vol. 242, pp. 114088. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1016/j.colsurfb.2024.114088
Abstrakt: Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG 5k -block-PCL 5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB's drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: