Single-walled carbon nanotube-assisted antibiotic delivery and imaging techniques
Inventors
Assignees
Publication Number
US-10898434-B2
Publication Date
2021-01-26
Expiration Date
2039-03-27
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Abstract
A new route is shown for at delivery in fighting drug resistant infections. Nanotubes and antibiotics and complexed non-covalently, with no chemical bonding, but through adsorption of antibiotics onto the nanotube surface governed by sufficiently strong molecular attraction between hydrophobic systems of the two. This allows the antibiotics to be freed from the nanotubes more easily as they reach the cell membrane. When antibiotics are introduced with nanotubes in this manner, bacterial resistance is mitigated by nanotube transport potentially into the membrane of the bacteria. Nanotubes used in this way help to overcome antibiotic resistance.
Core Innovation
The invention is directed toward the use of single-walled carbon nanotubes (SWCNTs) non-covalently complexed with antibiotics for the delivery and imaging of therapeutics to combat drug-resistant bacterial infections. It achieves this by leveraging strong molecular attraction between the hydrophobic regions of the antibiotics and the nanotube surfaces, allowing the antibiotics to adsorb onto SWCNTs without forming covalent bonds. As a result, the antibiotics can be more readily released at the site of the infection, improving their cellular uptake and efficacy.
The problem addressed concerns the failure of conventional antibiotics due to the rapid emergence and spread of antibiotic resistance among pathogens such as Staphylococcus epidermidis, which limits treatment efficacy and leads to severe infections. Current approaches focus on new drug development, efflux pump inhibitors, or immunotherapeutics, but there is a significant need for more effective drug delivery systems that can circumvent bacterial resistance mechanisms.
This invention demonstrates that SWCNTs complexed with antibiotics, specifically doxycycline and methicillin, enhance antibacterial activity compared to antibiotics alone, including in strains initially resistant to methicillin. The SWCNT/antibiotic complexes facilitate improved colony inhibition and antibacterial effects in Staphylococcus epidermidis. Furthermore, the inherent near-infrared fluorescence of SWCNTs enables the tracking of drug delivery and internalization within bacterial cells, adding an imaging capability to the therapeutic approach.
The method utilizes aqueous dispersions of SWCNTs non-covalently bound to antibiotic molecules, ensuring effective dispersion and potential preferential interaction with bacterial membranes. The system allows for improved delivery, potential to bypass antibiotic resistance, multifunctional tracking via fluorescence imaging, and applicability to multiple antibiotic classes, presenting a novel and synergistic route for enhancing antibiotic efficacy against resistant bacterial strains.
Claims Coverage
There are two independent claims in the patent, covering both a delivery device and a method for delivering antibiotics using single-walled carbon nanotubes.
Delivery device comprising SWCNTs complexed non-covalently with antibiotics
The device provides a substrate made of single-walled carbon nanotube (SWCNT) having a nanotube surface, where the selected antibiotic drug is complexed by non-covalently bonding (adsorption) to the SWCNT surface. The adsorption is governed by sufficiently strong molecular attraction between hydrophobic systems of the antibiotic and the carbon nanotube. - The antibiotics specified are doxycycline and methicillin. - The antibiotics are not chemically bonded but are adsorbed onto the nanotube surface.
Method for delivering antibiotics to treat bacterial infection using SWCNTs
The method involves providing SWCNTs as a substrate for the selected antibiotic drug, forming a non-covalent complex by adsorption of the antibiotic onto the nanotube surface through molecular attraction between hydrophobic systems, and administering the nanotube/drug hybrid to deliver the antibiotic to an antibiotic-resistant bacterial cell for therapeutic purpose. - The method includes delivery to a bacterial cell that is antibiotic resistant. - The use of doxycycline or methicillin as the antibiotic. - The complexation employs non-covalent bonding through adsorption.
The independent claims focus on a delivery device utilizing SWCNTs for non-covalent antibiotic adsorption and a method for administering such complexes to treat antibiotic-resistant bacteria, emphasizing non-covalent binding and delivery of doxycycline or methicillin using SWCNTs.
Stated Advantages
Enhanced antibacterial activity against drug-resistant bacteria, including those initially resistant to the antibiotic, when delivered via SWCNT/antibiotic complexes.
Ability to bypass or mitigate antibiotic resistance by facilitating delivery of antibiotics directly into bacterial cells.
Multifunctional capability for both therapeutic delivery and fluorescence-based imaging, enabling tracking of drug delivery inside bacterial cells.
SWCNTs exhibit low cytotoxicity when formulated with drug compounds, and SWCNT/antibiotic complexes show less inherent toxicity to human cells compared to antibiotics alone.
Potential to recycle or reuse existing antibiotics for treatment of new resistant bacterial infections.
Documented Applications
Delivery of antibiotics (doxycycline and methicillin) to treat infections caused by antibiotic-resistant Staphylococcus epidermidis.
Fluorescence imaging and tracking of antibiotics delivered to bacterial cells using single-walled carbon nanotube emission.
Use in therapeutic systems for overcoming limitations with existing drug therapies and combating antibiotic resistance.
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