Nanoparticles in Drug Delivery
Hansae, year 13 student.
Nanotechnology is an emerging field that makes use of matter on the atomic, molecular, and supramolecular scale for industrial purposes. It involves the ability to see and manipulate individual atoms and molecules in order to utilise its benefits such as increased safety and efficacy. Today’s scientists and engineers are researching how they could deliberately make materials at the nanoscale and take advantage of their enhanced properties such as higher strength, or lighter weight. With the potential to be applied to various fields, researchers have found a new way to revolutionise drug delivery using nanoparticles.
Design of Nanotechnology
In the field of medicine, nanoparticles have the potential to improve the stability and solubility of encapsulated drugs by promoting transport across membranes. This links to many other advantages of utilising nanoparticles. For example, nanoparticles can be used in targeted drug delivery at the site of disease in order to improve the uptake of poorly soluble drugs, and the targeting of drugs to a specific site. Nanoparticles also allow prolonged circulation times which increases the safety and efficiency of using nanoparticles.
New research has utilised advancements in controlled synthesis strategies to incorporate complex architectures, bio-responsive moieties and targeting agents to enhance the delivery of medicine with nanoparticles. Precision medicine significantly improved the delivery of medicine because of its accuracy and the change in its size, surface charge, lipid composition, number of lamellae and surface modifications.
There are in total three different classes of nanoparticles.
1. Lipid-based nanoparticles
Lipid-based nanoparticles include various forms, but spherical forms with at least one lipid bilayer surrounding at least one internal aqueous compartment are the most common one. Some of its advantages are formation simplicity, self-assembly, biocompatibility, ability to carry large payloads and a range of physicochemical properties that can be controlled to maintain their biological characteristics. For these reasons, lipid-based nanoparticles are one of the most promising and common FDA approved, colloidal carriers for bioactive organic molecules.
For liposomes, which are defined as one of the subsets of lipid-based nanoparticles that have the most members, the nanoparticles are typically composed of phospholipids. These can form unilamellar and multilamellar vesicular structures. Unilamellar vesicles are spherical chambers, bounded by a single bilayer of an amphiphilic (having both hydrophilic, and hydrophobic parts) lipid, containing an aqueous solution inside them. These features allow the liposome to carry and deliver hydrophilic, hydrophobic and lipophilic drugs. Furthermore, they can entrap hydrophilic and lipophilic compounds in the same system, which expands their use. These features played a part in altering the nanoparticles’ size, surface charge, lipid composition, number of lamellae and surface modifications.
LNPs, which stand for lipid nanoparticles, are liposome-like structures widely used for the delivery of nucleic acids. One difference between LNPs and traditional liposomes is that LNPS can form micellar structures within the particle core, which can be altered based on formulation and synthesis parameters. There are four major components that make up LNPs: cationic/ionizable lipids that are complex with negatively charged material and aid endosomal escape, phospholipids for particle structure, cholesterol for stability and membrane fusion and PEGylated lipids to improve stability and circulation. The efficiency of their nucleic acid delivery along with their simple synthesis, small size and serum stability have made LNPs particularly important in personalised genetic therapy applications. Because ionizable LNPs have a near-neutral charge at physiological pH, but become charged in acidic endosomal compartments, they are an ideal platform for the delivery of these nucleic acid therapies. Despite these advantages, LNPs can still be limited by low drug loading and biodistribution which may result in high uptake to the liver.
2. Polymeric nanoparticles
Polymeric nanoparticles can be synthesised from natural or synthetic materials, as well as monomers or preformed polymers. Thus, it is possible for polymeric nanoparticles to have a wide variety of possible structures and characteristics. This type of nanoparticles can be formulated to enable precise control of multiple nanoparticle features and are generally good delivery vehicles since they are biocompatible and have simple formulation parameters. They are synthesised using various techniques such as emulsification, nanoprecipitation, ionic gelation, and microfluidics, and these all result in different final products. Moreover, they also have variable drug delivery capabilities which enable delivery of various payloads including hydrophobic and hydrophilic compounds. These can also be used with different molecular weights such as small molecules, biological macromolecules, proteins, and vaccines.
Two of the most common forms of polymeric nanoparticles are nanocapsules and nanospheres. Within these two large categories, nanoparticles can be divided further into shapes. They all have varying sizes, shapes, and surface areas, but are still very effective vehicles for the delivery of therapeutics.
However, due to the varying characteristics of each nanoparticle, the chemistry needs to be highly controlled. Active functional groups present on the exterior of dendrimers enable the conjugation of biomolecules. Features such as Polyelectrolytes have been incorporated in numerous nanoparticle formulations to improve properties such as bioavailability and mucosal transport. They can also be useful for intracellular delivery since they are inherently responsive to stimuli.
In conclusion, polymeric nanoparticles are the ideal candidates for drug delivery thanks to their biodegradable, water-soluble, biocompatible, biomimetic and stable features. The modification of surfaces is easy and this allows them to deliver drugs, proteins, and genetic materials to targeted tissues. If developed fully, they can be useful in cancer medicine, gene therapy and diagnostics. However, at this stage of development, there are still some disadvantages, which include an increased risk of particle aggregation and toxicity.
3. Inorganic nanoparticles
Other than lipids, or synthetic materials, nanoparticles can be made of inorganic materials such as gold, iron, and silica. These inorganic nanoparticles are precisely formulated and can be engineered to have a wide variety of sizes, structures, and geometrics for targeted drug delivery. Gold nanoparticles (AuNPs) are the most well-studied and are used in various forms, including nanospheres, nanorods, nanostars, nanoshells, and nanocages. In addition, they can have unique physical, electrical, magnetic and optical properties due to the properties of the base material itself. They are also easily functionalized, which gives them additional properties and delivery capabilities.
Iron oxide is another commonly researched material for inorganic nanoparticle synthesis, and they make up the majority of FDA-approved inorganic nanomedicines. In numerous experiments, magnetic iron oxide nanoparticles have shown success as contrast agents, drug delivery vehicles and thermal-based therapeutics. Other common inorganic nanoparticles include calcium phosphate and mesoporous silica, and they both have been used successfully for gene and drug delivery. Quantum dots are unique nanoparticles used primarily in vitro imaging applications, but they also show promising potential for in vivo diagnostics. Due to their magnetic, radioactive or plasmonic properties, inorganic nanoparticles are uniquely qualified for applications such as diagnostics, imaging and photothermal therapies. Even though most of them have good biocompatibility and stability, they are still limited in their clinical application due to low solubility and toxicity concerns.
The field of nanoparticles is a very promising field with multiple potential branches of development. Certain types of nanoparticles are close to being used in everyday life, but some biological barriers need to be broken for nanoparticles to be able to be adopted safely.
Suri, S., Fenniri, H. and Singh, B. (2007). Nanotechnology-based drug delivery systems. Journal of Occupational Medicine and Toxicology, 2(1), p.16. doi:10.1186/1745-6673-2-16.
Mitchell, M.J., Billingsley, M.M., Haley, R.M., Wechsler, M.E., Peppas, N.A. and Langer, R. (2020). Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, [online] 20, pp.1–24. doi:10.1038/s41573-020-0090-8. WallpaperAccess. (n.d.). Awesome Nanotechnology
Wallpapers. [online] Available at: https://wallpaperaccess.com/nanotechnology [Accessed 9 Jan. 2023].
Written by Hansae, a Year 13 student