Antibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Maurer, Christine K
de Rossi, Chiara
Hartmann, Rolf W
MetadataShow full item record
AbstractCystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model. SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall, nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate significance in the area of nano-based delivery of novel anti-infectives.
CitationAntibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. 2014, 192:131-40 J Control Release
The following license files are associated with this item:
- Pseudomonas aeruginosa pyocyanin production reduced by quorum-sensing inhibiting nanocarriers.
- Authors: Lu HD, Pearson E, Ristroph KD, Duncan GA, Ensign LM, Suk JS, Hanes J, Prud'homme RK
- Issue date: 2018 Jun 10
- Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model.
- Authors: Luo J, Dong B, Wang K, Cai S, Liu T, Cheng X, Lei D, Chen Y, Li Y, Kong J, Chen Y
- Issue date: 2017
- Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis.
- Authors: Pastor M, Moreno-Sastre M, Esquisabel A, Sans E, Viñas M, Bachiller D, Asensio VJ, Pozo AD, Gainza E, Pedraz JL
- Issue date: 2014 Dec 30
- Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor.
- Authors: Furiga A, Lajoie B, El Hage S, Baziard G, Roques C
- Issue date: 2015 Dec 28
- Inhibition of quorum-sensing-dependent virulence factors and biofilm formation of clinical and environmental Pseudomonas aeruginosa strains by ZnO nanoparticles.
- Authors: García-Lara B, Saucedo-Mora MÁ, Roldán-Sánchez JA, Pérez-Eretza B, Ramasamy M, Lee J, Coria-Jimenez R, Tapia M, Varela-Guerrero V, García-Contreras R
- Issue date: 2015 Sep