Of all the fields where nanotechnology is making an impact, drug delivery may be the one most revolutionized by these tiny technologies. Drug delivery has traditionally been a complex challenge, often impeded by the limited solubility, stability, and bioavailability of therapeutic agents. Nano-sized drug delivery systems (DDS) have emerged as a major breakthrough in pharmaceutical science by offering a dynamic range of solutions to treat some of the most serious conditions affecting human health today.
Why are nanoparticles so valuable for DDS? Their high surface area-to-volume ratio and their chemical and geometric tunability are key factors. Their size also plays an important role — nano-sized structures stay in the bloodstream for long periods of time, allowing for the sustained release of incorporated drugs. Nanoscale DDS can also better penetrate tissues than larger molecules, thereby facilitating drug uptake by cells and ensuring activity at the targeted location. This efficiency reduces side effects.
We analyzed the CAS Content CollectionTM, the largest repository of curated scientific information, to better understand current research trends in nanoscale DDS and how these systems are being used to treat various diseases. Interest in nano DDS has skyrocketed in recent years, with DDS outpacing publications in other nanotechnology fields (see Figure 1).
Our analysis demonstrates that many nanotechnology forms and materials are making progress as treatments for different conditions. Patent publications have yet to catch up to journal publications, suggesting that the transition to clinical usage is just beginning. However, the future of nano DDS looks bright.
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Targeted diseases and nano DDS
Nanotechnology in medicine has been evolving at a rapid pace. A tremendous amount of research in recent years has reported diagnostic and therapeutic applications of nanotechnology, some of which have reached advanced clinical trials and even approval. The CAS Content Collection reveals the breadth of conditions and disorders to which nanotechnology may be applied (see Figure 2).
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Some of the most significant conditions addressed in recent research include:
Cancer
One of the most promising uses of nano DDS is to target cancer cells because nanocarriers can attack tumors with large doses of a given drug. This augments efficacy while protecting normal cells from excessive toxicity and the resulting side effects for patients.
Nano DDS can target cancer cells passively by exploiting the enhanced vascular permeability and weakened lymphatic drainage of cancer cells, or they can do so actively by targeting the interaction between ligand and cellular receptors. Nanoparticles can also be used to induce therapeutic hyperthermia or localized heating within tumors. Hyperthermia can be driven by laser radiation or an applied magnetic field; magnetic nanoparticles also act as heating mediators.
Nanoparticles of noble metals, which have unique optical properties, have been used for inventive light-based treatments for cancer. Inorganic nanoparticles have multiple applications in cancer care. Iron oxide nanoparticles, for example, can be used as contrast agents for MRIs, thereby tracking immune cell migration. Silver nanoparticles are known to enhance the effects of cancer drugs in combination therapies, which allows for lower doses to reduce cytotoxic effects. Carbon nanotubes have also been used as nanocarriers for cancer drugs, but researchers are still exploring how to ensure safety and biodegradability with them.
Exosomes are increasingly garnering interest for cancer immunotherapy treatments. Whether tumor-derived, composing tumor-associated antigens, or derived from dendritic cells presenting antigens, exosomes can trigger immune activation and be used in developing anti-cancer vaccines.
Genetic disorders
Gene-based therapies must cross multiple biological barriers while avoiding degradation. Nanoparticles are uniquely suited to these applications. A number of nanostructures including lipid, polymeric, and various inorganic nanocarriers can incorporate certain genetic materials, such as plasmid DNA, mRNA, and siRNA. One of the most significant applications for nano-based gene delivery is the use of nanoparticles in genetic-based vaccines.
Lipid-based nanoparticles are an important subsection of nano DDS research (see Figure 3). A major advantage of them as drug carriers is that most of their components are physiological lipids and excipients which are generally recognized as safe (GRAS). This makes them superior to other nano-sized drug delivery systems in minimizing systemic toxicity. Their elegance lies in their ability to overcome some of the most pressing challenges in drug delivery — improving the solubility of poorly water-soluble drugs, protecting labile compounds from degradation, and precisely targeting disease sites within the body.
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Autoimmune diseases
Current treatments for autoimmune diseases involve broad-spectrum, nonspecific anti-inflammatory, or immunosuppressive drugs. These can alleviate clinical symptoms, but they don’t target the underlying causes of autoimmune conditions, and they can have serious side effects by suppressing the body’s immune system.
Nanocarrier-based drug delivery, however, can increase the efficiency of inducing antigen-specific tolerance in vivo. This strategy can be used to treat rheumatoid arthritis, multiple sclerosis, and lupus, and it could play an important role in preventing immune system rejection of transplanted organs.
Inflammatory conditions
Inflammation is a common feature of many diseases, and in some conditions, it can reach the point of contributing to disease pathogenesis. Targeting inflammation by using nanomedicines, either through the detection of molecules overexpressed onto the surface of activated macrophages or endothelial cells or via enhanced blood vessel permeability provides a promising solution for the treatment of inflammatory diseases. Various types of nanocarriers have been or are being developed for the management of inflammation, including liposomes, polymer nanoparticles, micelles, dendrimers, and hydrogel-based formulations.
Infectious diseases
Nano DDS show potential in treating numerous viral and bacterial infections because they offer straightforward treatment regimens with lower dose frequency. For example, injectable nanoparticles containing antiretroviral drugs are a novel treatment method for delivering medication to HIV patients. This delivery method reduces dose frequency for patients, and it may even be useful as a preventative measure.
Nanocarriers may also be used as vaccine delivery mechanisms, particularly lipid nanoparticles and nanoemulsions. Cationic lipid nanoparticles were successfully used in recent mRNA vaccines for COVID-19. Nanoemulsions are promising drug delivery vehicles for hydrophobic drugs and could be important breakthroughs as adjuvants for vaccines. Bacterial infections may also be treated with nano DDS, including antibiotic-resistant bacteria. As a novel delivery method, nano DDS can target bacteria and deliver high doses of antibiotics. Repurposing known classes of antibiotics into nano DDS has been found to overcome resistance mechanisms, and this could mark significant progress in treating multi-drug-resistant infections.
Challenges and future directions for nano DDS
Nano DDS are not without challenges, however. Researchers are working to understand toxicity risks and long-term safety concerns. Scaling up production and successfully completing clinical trials are also important factors in bringing these treatments into widespread clinical usage.
Despite these roadblocks, nano DDS offer the chance to make medicine more precise and personalized. As our analysis shows, research has already made significant progress in realizing the many benefits of nano DDS, and with continued innovation, these microscopic treatments can overcome long-standing issues with drug delivery, signaling new breakthroughs for patients.
To learn more about how innovations in nanotechnology are advancing other fields including energy, electronics, and healthcare, explore our recent CAS Insights Report.