A new antibacterial drug-delivery system developed

The nanoconjugates will be useful for cancer patients suffering from bacterial infections

A new antibiotic drug-delivery system that improves the efficacy of drugs thereby reducing the dosage used for treating bacterial infections has been tested in a lab by researchers. A peptide, which has not been approved for clinical use, bound to gold nanoparticles was able to kill E. coli and Salmonella typhi more efficiently at lower dosages.

“Drug delivery becomes better and the bioavailability improves when the drug is conjugated [bound] to gold nanoparticles. So reduced dosage is sufficient to kill the bacteria. Reducing the dosage of antibiotics used is one of the strategies to reduce the possibility of drug resistance setting in,” says the Dr.

Bioavailability

The peptide in a free form may not be bioavailable as it gets degraded relatively fast. In a free form, the peptide is also not able to effectively kill the bacteria by engaging with the bacterial membrane and disrupting it, while the nanoconjugate fares better on these counts.

The challenge was to arrive at an optimum number of peptides that are bound to nanoparticles to get the best results. When there are too few or too many peptides bound to the nanoparticles the antibacterial activity gets compromised. “There is significant antibacterial activity when about 1000 peptides are bound to a nanoparticle,” says Dr.

The peptide called sushi-peptide bound to nanoparticles was able to kill 50% of bacteria at much lower concentration (400 nM) while the free peptide’s antibacterial activity was not significant at the same concentration, says one of the  authors of the paper.

Besides normal cells infected with bacteria, the peptide bound to nanoparticles will be particularly useful in the case of cancer patients suffering from bacterial infections. “Rapid metabolism at the cancer site sucks all nutrients and leads to nutritional deficit in the body. When chemotherapy is given even the bacteria already present in the body but kept under check become disease-causing,” says a cancer specialist

After chemotherapy the immunological response gets damaged as cells responsible for protecting against bacteria are reduced in number. So the person becomes vulnerable to infection. “Antibiotics by itself cannot kill all the bacteria. The inherent immunological response should be able to challenge the bacteria once antibiotic treatment is completed. Since this does not happen, the bacteria develop drug resistance,” says Dr.

Folate receptors

Specific receptors called folate receptors are present in large numbers on the surface of cancer cells. Folic acid added to the nanoconjugates is recognised by these receptors and help in the binding process. “Once the nanoconjugates enter the cancer cells they interact with the bacteria and kill them by disrupting the cell membrane. The nanoconjugates have 40% better antibacterial activity compared with free peptides,” says one of the authors of the paper.

The nanoconjugate is not toxic to cancer cells and targets only the bacteria.

“We would next like to study if our nanoconjugates can be used on antibiotic-resistant strains and also understand the fate of gold nanoparticles used for making the nanoconjugates,” says Dr.  Instead of gold nanoparticle, biodegradable polymers can be used. The only condition is that the peptide should be able to interact with the bacterial membrane. A few more studies have to be carried out before the nanoconjugate can be tested on animals.

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New method removes nanoparticles from blood with ease

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 A team of US engineers has developed a new technology that uses an electrical field to easily and quickly isolate drug-delivery nano-particles from the blood.

The electronic chip can also serve as a tool to separate and recover nano-particles from other complex fluids for medical, environmental and industrial applications.

Nano-particles, which are generally one thousand times smaller than the width of a human hair, are difficult to separate from plasma — the liquid component of blood — owing to their small size and low density.

Traditional methods to remove nano-particles from plasma samples typically involve diluting plasma.

These methods either alter the normal behaviour of the nano-particles or cannot be applied to some of the most common nano-particle types.

"This is the first example of isolating a wide range of nano-particles out of plasma with a minimum amount of manipulation," said Stuart Ibsen, post-doctoral fellow at University of California, San Diego.

"We have designed a very versatile technique that can be used to recover nano-particles in a lot of different processes," he added.

The new nano-particle separation technology will enable researchers better monitor what happens to nano-particles circulating in a patient's bloodstream.

Scientists can also use this technology in the clinic to determine if the blood chemistry of a particular patient is compatible with the surfaces of certain drug-delivery nano-particles.

The chip contains hundreds of tiny electrodes that generate a rapidly oscillating electric field that selectively pulls the nano-particles out of a plasma sample.

"It's amazing that this method works without any modifications to the plasma samples or to the nano-particles," Ibsen noted in the study published in the journal Small.