In recent years, nanotechnology has revolutionized the field of drug delivery, specifically, through the utilization of nanogels. Here, we will explore the usage, potential benefits, and future prospects of nanogels, of which there are many.
Image Credit: Yurchanka Siarhei/Shutterstock.com
What are Nanogels and How Do They Work?
A nanogel is a hydrogel where the particles are in the nanoscale size range and a hydrogel is a three-dimensional network of a polymer that is cross-linked and hydrophilic. Due to their hydrophilic nature, nanogels can swell, which is the reason that they can hold such large amounts of water.
One vital attribute of nanogels is that their properties can be modified by altering their composition.
Nanogels have many promising applications, such as in gene delivery and medical imaging; here, the application of triggered drug delivery will be considered.
In general, nanogels can entrap at least 30% wt. of drugs, through various interactions, as they are amply swollen. The drug assimilation leads to the collapse of the gel and the formation of stable nanoparticles, which keep the drug inside.
As hydrophilic polymer chains at the surface become exposed, a protective layer is formed around the gel and this layer can be functionalized to target specific tissue or cells. Evidently, the compositional design and the chemistry of a nanogel are critical to its value as a triggered drug delivery system to a particular target.
Drug Delivery with PEG-PEI
An example of a specific nanogel is PEG-PEI (poly(ethylene glycol)-polyethyleneimine), which was the first nanogel to be introduced in 1999.
Overall, PEG-PEI nanogels are greatly biocompatible, and this is due to the PEG, since PEI has been shown to be cytotoxic.
PEG has demonstrated non-toxic, and non-immunogenic properties, therefore, its inclusion allows the overall material to be more soluble in water and less toxic, and thus more biocompatible, than if PEI was used alone.
There is a multitude of properties, such as size, that are important to be aware of as they are vital in determining a nanogel’s potential application and its effectiveness as a drug release system.
PEG-PEI nanogel particles are small in size (20-220 nm) and it is likely that this results in enhanced infiltration of tissues and cells, meaning that the drug is more likely to have an effect on its target.
Another vital property of nanogels is their charge, as this will affect the degree of interaction between nanogel and drug, and hence will determine the rate at which the drug is released.
PEI has a high (positive) charge density, therefore making it the perfect vessel for negatively charged drugs and biological components. Furthermore, the charge density can be modified by pH, thus the release rate can be controlled as the strength of the drug-nanogel interaction can be varied.
The applications of PEG-PEI nanogels in drug release systems show great promise and have the potential to have a massive impact in the biomedical field.
One study encapsulated a new anti-cancer drug, targeted at pancreatic cancer, namely AQ10 (6-(hydroxymethyl)-1,4- anthracenedione (AQ) analogue), into a PEG-PEI nanogel. A comparison was made between using the drug with or without the nanogel, and it was found that when the nanogel was used in conjunction with the drug, cell growth was more effectively reduced, which is the desirable outcome for cancer treatments. The study concluded that the usage of this nanogel as a drug delivery device was successful, since the nanogel allowed cells to become more susceptible to the drug.
Another study used PEG-PEI nanogel to explore the delivery of SODN (antisense phosphorothioate oligonucleotides) to multidrug-resistant (MDR) human oral epidermoid carcinoma cells. Overall, the study observed that when the drug was accompanied by PEG-PEI nanogel, it was more likely to successfully accumulate in the carcinoma cells. This study is especially noteworthy as it signifies the introduction of nanogels, hence providing a baseline for all subsequent nanogel research, whether PEG-PEI-based or not.
Advantages and Disadvantages of Nanogels
A major advantage of nanogels is their size, as they provide a large specific surface area, therefore increasing potential interaction within vivo components. This is beneficial as the drug is more likely to meet the target area, and thus execute its desired effect. Furthermore, due to the tunability of nanogels, they can be modified to be employed for a range of applications. For example, one study functionalized the surface of PEG-PEI by introducing an amine group and this allowed the nanogel to be used for spinal cord injury treatment, thereby demonstrating the wide and varied potential for nanogels.
The disadvantages of nanogels in drug delivery are sparse. One example is that the release rate can be too fast as it is diffusion-based. However, various research has focused on remedying this by ensuring that there is an interaction between drug and gel, therefore delaying the release.
A key benefit to nanogels is that the research is constantly evolving, so when a potential drawback is identified, a solution is promptly suggested and investigated, such as the example given.
In summary, it can be concluded that nanogel particles are an ideal platform for triggered drug delivery due to the way they can be manipulated. This allows them to possess desirable properties for an array of targeted release systems.
As discussed, current research supports the efficacy of PEG-PEI nanogels, and others, in triggered drug delivery, however, although nanogel research has progressed substantially over the years, there is a need for further exploration before clinical application.
References and Further Reading
Soni, K., Desale, S. and Bronich, T., (2016) Nanogels: An overview of properties, biomedical applications and obstacles to clinical translation. Journal of Controlled Release, 240, pp.109-126. https://doi.org/10.1016/j.jconrel.2015.11.009
Vinogradov, S., Batrakova, E. and Kabanov, A., (1999) Poly(ethylene glycol)– polyethyleneimine NanoGel™ particles: novel drug delivery systems for antisense oligonucleotides. Colloids and Surfaces B: Biointerfaces, 16(1-4), pp.291-304. https://doi.org/10.1016/S0927-7765(99)00080-6
Mauri, E., Chincarini, G., Rigamonti, R., Magagnin, L., Sacchetti, A. and Rossi, F., (2017) Modulation of electrostatic interactions to improve controlled drug delivery from nanogels. Materials Science and Engineering: C, 72, pp.308-315. https://doi.org/10.1016/j.msec.2016.11.081
Pinelli, F., Pizzetti, F., Ortolà, Ó., Marchetti, A., Rossetti, A., Sacchetti, A. and Rossi, F., (2020) Influence of the Core Formulation on Features and Drug Delivery Ability of Carbamate-Based Nanogels. International Journal of Molecular Sciences, 21(18), p.6621. https://doi.org/10.3390/ijms21186621
Pinelli, F., Pizzetti, F., Rossetti, A., Posel, Z., Masi, M., Sacchetti, A., Posocco, P. and Rossi, F., (2021) Effect of surface decoration on properties and drug release ability of nanogels. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 614, p.126164. https://doi.org/10.1016/j.colsurfa.2021.126164
Ganta, C., Shi, A., Battina, S., Pyle, M., Rana, S., Hua, D., Tamura, M. and Troyer, D., (2008) Combination of Nanogel Polyethylene Glycol-Polyethylenimine and 6(hydroxymethyl)-1,4-anthracenedione as an Anticancer Nanomedicine. Journal of Nanoscience and Nanotechnology, 8(5), pp.2334-2340. https://doi.org/10.1166/jnn.2008.294
Vismara, I., Papa, S., Veneruso, V., Mauri, E., Mariani, A., De Paola, M., Affatato, R., Rossetti, A., Sponchioni, M., Moscatelli, D., Sacchetti, A., Rossi, F., Forloni, G. and Veglianese, P., (2019) Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury. ACS Nano, 14(1), pp.360-371. https://doi.org/10.1021/acsnano.9b05579