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Nanogels have emerged over the last few years as an effective vessel for carrying and releasing drugs to patients and have since become one of the many parts of nanomedicine—the interface where nanotechnology, medicine and pharmaceuticals have merged together to create their own defined field. In this article, we look at these innovative drug delivery systems in more detail.
Nanogels, in essence, are a nanosized hydrogel. A hydrogel is a polymer-based gel that is constructed by crosslinking polymer chains together to form a macromolecular network. There are many ways in which hydrogels can be synthesized, but the polymeric monomers need to be synthesized, followed by being further polymerized with functional cross-linker molecules to create a ‘net-like’ polymer structure. Because the gels contain pores, these pores can be loaded with drugs that can then be released later. Nanogels are essentially the same thing but are on the scale of 20-200 nm. Most nanogels are synthesized via some form of emulsion polymerization reaction.
Researchers and/or clinicians can introduce nanogels to patients through a variety of routes, including oral, pulmonary, nasal, parenteral and intra-ocular routes. The drugs are released from the nanogels in a number of ways, but the release mechanism is caused by an external stimulus that initiates an internal property change. This property change causes the polymer network to either swell or contract (depending on the release mechanism), and this physical change causes the drug payload to be released to the target area. This stimulus can either arise from the direct environments within the body or an external stimulus source can cause this physical change to happen—which again depends on the type of release mechanism. The most common internal environmental conditions that cause a physical change are a specific pH and a change in temperature within a specific volume (also known as the volume phase transition temperature). On the other hand, the most common external stimulus is light which causes photochemical and photoisomerization reactions to occur—which releases the drug payload.
The applications of nanogels in medicine are widespread, and include being used in local anaesthetics, as anti-inflammatory agents, in the delivery of vaccines, in transdermal drug deliveries, in bone regeneration treatments, for delivering insulin (for diabetic patients), in ophthalmology applications, and in the treatment of cancers, autoimmune diseases, neurodegenerative diseases, and microbial infections.
Nanogels can be classified by different means, depending on how they react to a stimulus or what types of cross-linkages are present within the nanogel. On the stimulus front, nanogels can be classified as either non-responsive or stimuli-responsive. Non-responsive nanogels are nanogels which swell in the presence of water (due to water absorption), whereas stimuli-responsive nanogels will swell due to another environmental condition. These conditions can be pH, magnetic field, ionic strength, or temperature, and a nanogel which is responsive to more than one stimulus is termed a multi-responsive nanogel.
The other type of classification is based around the types of cross-linking, and the two categories are physically cross-linked nanogels and chemically cross-linked nanogels. Physically cross-linked nanogels are nanogels which are held in place by weak intermolecular interactions, such as van der Waals forces, hydrogen bonds, hydrophobic interactions, or electrostatic interactions, and include liposome modified nanogels, micellar nanogels and hybrid nanogels. Chemically cross-linked nanogels, on the other hand, are nanogels where the cross-links are chemically bonded to the monomer chains through strong covalent bonds. The strength of chemically cross-linked nanogels are highly dependent on the functional groups within the nanogel network.
Properties of Nanogels
Nanogels possess a wide range of properties and this makes them an effective drug delivery vessel. First off, they are highly biocompatible and highly biodegradable. These are two key properties for any drug delivery system, as it means that they won’t be attacked by the body’s immune system and they can also be broken down excreted by the body when the drug payload has been released. Nanogels are also inert in the blood stream which means that they won’t induce any response by the body in either the bloodstream or in the tissue fluid.
Nanogels have an inherent small size and this brings about its own set of beneficial properties. This small size means that nanogels have a high permeation capability, are able to avoid rapid renal exclusion, are able to avoid phagocytic cells, are able to avoid being uptaken by the reticuloendothelial system, a high ability to penetrate the endothelium in pathological sites (tumors, infected regions etc), a high capillary permeability, as well as having the capability to cross the blood brain barrier (BBB) and reach areas that are not accessible by hydrogels.
As mentioned, nanogels are also designed with the ability to swell or contract in the presence of a stimulus. The properties in this regard vary from nanogel to nanogel and depend on the polymers (and cross-linkers) used. So, all nanogels are responsive to something (even if it is water) and this is a key property that enables them to deliver drugs. Many nanogels can also be conjugated with functional groups and/or antibodies which enables them to be used in targeted drug delivery approaches.
Sources and Further Reading
“Nanogels as Novel Drug Delivery Systems - A Review”- Yadav H. K. S. et al, Journal of Pharmacy and Pharmaceutical Research, 2017