WS15.6 Development of nanomedicines for the treatment of pulmonary biofilm infections: Insights from advanced fluorescence microscopy studies

Forier, Katrien; Messiaen, Anne-Sophie; Risseeuw, Martijn; Calenbergh, S. Van; Deschout, Hendrik; Raemdonck, Koen; Nelis, Hans; Danhier, Fabienne; Préat, Véronique; Baets, Frans De; Smedt, Stefaan De; Demeester, Joseph; Coenye, Tom; Braeckmans, Kevin

doi:10.1016/s1569-1993(13)60094-6

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“…Negatively charged liposomes consisting of the neutral phospholipid 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) and the anionic phospholipid 1,2-dipalmitoyl- sn -glycero-3-phospho-(1′- rac -glycerol) (DPPG) were prepared by the Thin Film Hydration (TFH) method as described before [19]. After mixing the two lipids in a molar ratio of 8:2 and final lipid concentration of 20 mg mL −1 , a thin lipid film was created by rotary evaporation (Vaccubrand PC 2001, Wertheim, Germany) at 50 °C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Exploring Light-Sensitive Nanocarriers for Simultaneous Triggered Antibiotic Release and Disruption of Biofilms Upon Generation of Laser-Induced Vapor Nanobubbles

et al. 2019

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Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard.

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Section: Methodsmentioning

confidence: 99%