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Abstract
The antimicrobial resistance crisis requires novel approaches for the therapy of infections especially with Gram-negative pathogens. Pseudomonas aeruginosa is defined as priority 1 pathogen by the WHO and thus of particular interest. Its drug resistance is primarily associated with biofilm formation and essential constituents of its extracellular biofilm matrix are the two lectins, LecA and LecB. Here, we report microbial lectin-specific targeted nanovehicles based on liposomes. LecA- and LecB-targeted phospholipids were synthesized and used for the preparation of liposomes. These liposomes with varying surface ligand density were then analyzed for their competitive and direct lectin binding activity. We have further developed a microfluidic device that allowed the optical detection of the targeting process to the bacterial lectins. Our data showed that the targeted liposomes are specifically binding to their respective lectin and remain firmly attached to surfaces containing these lectins. This synthetic and biophysical study provides the basis for future application in targeted antibiotic delivery to overcome antimicrobial resistance.
Highlights
IntroductionThe formulation of antibiotics as nanomedicines[4,5,6,7] has been widely studied to overcome the different limitations of the free drugs, such as toxicity, solubility and bioavailability associated with sustained drug release,[8] efficient mucus penetration[9] and the ability of some formulations, e.g. liposomes, to fuse with the bacterial cell envelopes.[10,11] Especially the liposomes have evolved as potent nanovehicles for antimicrobials.[6] Arikayce (Insmed, Inc.), the liposomal formulation of amikacin, has been recently approved by the FDA for the treatment of Mycobacterium avium complex (MAC) lung infections
Helmholtz Centre for Infection Research, 66123 Saarbrucken, Germany e Department of Pharmacy, Saarland University, 66123 Saarbrucken, Germany f KIST Europe, 66123 Saarbrucken, Germany g Department of Systems Engineering, Saarland University, 66123 Saarbrucken, Germany h INM – Leibniz Institute for New Materials, 66123 Saarbrucken, Germany † Electronic supplementary information (ESI) available
We demonstrated that the targeted liposomes are retained on a lectin-coated surface from a passing liquid stream
Summary
The formulation of antibiotics as nanomedicines[4,5,6,7] has been widely studied to overcome the different limitations of the free drugs, such as toxicity, solubility and bioavailability associated with sustained drug release,[8] efficient mucus penetration[9] and the ability of some formulations, e.g. liposomes, to fuse with the bacterial cell envelopes.[10,11] Especially the liposomes have evolved as potent nanovehicles for antimicrobials.[6] Arikayce (Insmed, Inc.), the liposomal formulation of amikacin, has been recently approved by the FDA for the treatment of Mycobacterium avium complex (MAC) lung infections. Large amounts can be loaded into the inner sphere to overcome low drug solubility and provide stability under physiological conditions
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