Researchers may soon have the capacity to deliver drugs encapsulated in nanogels. These nanogels have great potential within the pharmaceutical industry and can reduce the side-effects of drugs without reducing effectiveness.
Researchers globally have long been working towards developing nanogels that can encapsulate drugs. These nanogels can contain antibiotics or other classes of drugs, which can then be administered to patients.
Previous studies with nanogels have shown that they reduce the toxicity of drugs without diminishing their effectiveness.
This means that the dose can sometimes even be increased to improve effectiveness or that drugs normally causing excessive side-effects can be used without greater risk.
Now researchers have taken this one step further and shown how the structure of a drug encapsulated in the nanogels affects the rate of release.
“In collaboration with researchers from the University of British Columbia in Vancouver, Canada we previously showed that we could quadruple the amount of an antimicrobial substance that we gave to mice, providing greater effectiveness but without more side-effects. This makes the nanogels an exciting new way of administering drugs. Our latest study shows how to regulate the release of the substances encapsulated in the nanogels,” explains a researcher behind the project, Hanne Mørck Nielsen, Professor, Department of Pharmacy, University of Copenhagen, Denmark.
The research has been published in the Journal of Colloid and Interface Science.
Nanogels are harmless
Nanogels are microfluidic self-assembled soft structures 100–200 nanometres in diameter, which are enabled by controlling the polymers that encapsulate active ingredients, by the actual active ingredient and by the method of preparation.
The polymer used is an octenyl succinic anhydride–modified version of hyaluronic acid, a natural substance that is both biodegradable and known for its beneficial effects in moisturising skin, and it does not harm the human body.
Previous experiments found that the size of the nanogels changed when some types of drugs were encapsulated but not for other drugs.
In the new study, the researchers aimed to find out what determines whether the nanogels change structure or not and the effects.
“The purpose of this research was to show not only that the polymers assemble into a spherical shape that encapsulates a large quantity of peptide but also how this affects the characteristics of the nanogels when even slightly structurally different peptides are encapsulated,” says Hanne Mørck Nielsen.
Peptide characteristics strongly influence nanogel function
The researchers inserted various peptides into the nanogels. Peptides, similar to the somewhat larger proteins, comprise various amino acids in sequence.
The researchers tested many peptides with the same length and charge but with different amino acid sequences, which affected the degree and positioning of the hydrophilic parts of the peptides.
The experiment showed that the size of the nanogels depends strongly on what molecule the researchers encapsulated in them. Some grew and others shrunk. They also differed in how much peptide could fit in each nanogel.
The researchers also used small-angle neutron scattering to determine the structure of each individual nanogel. The main difference was that the more hydrophobic peptides tended to be located internally rather than on the surface of the nanogel. When this happens, the nanogels become smaller.
“We also found that the structure of the peptides influences the rate of peptide release from the nanogel. Here, the slightly hydrophobic peptides have slower release kinetics than the just slightly more hydrophilic ones. The results show that one size does not fit all when encapsulating drugs in a nanogel. This knowledge offers better opportunities for better matching peptides with the nanogels to achieve the desired effect,” notes Hanne Mørck Nielsen.
Relevant for insulin and antibiotics
According to Hanne Mørck Nielsen, the study contributes to improving understanding of how nanogels can be used to encapsulate drugs. She says that a slightly more hydrophobic peptide might be useful if you want it to be released slowly in the body to minimise side-effects or to be effective for longer.
For example, this could apply to some types of insulin, for which the desired effect is over several hours or days.
“Using nanogels enables us to adjust the release profile of a drug for a longer-lasting effect or to use a higher dose of it without side-effects. This is the potential, and it may be very important in relation to many types of treatment, including antibiotics, for which a longer-lasting effect of an antibiotic in, for example, the nasal mucosa may be desired. In that situation, the nanogels can release an antibiotic slowly, which both kills the bacteria and keeps them away, without the body being overloaded with the negative effects of a large quantity of antibiotics,” concludes Hanne Mørck Nielsen.
