The nano revolution: pioneering the next frontier in drug delivery systems

In this article, Rumiana Tenchov (pictured), Information Scientist at CAS, a division of the American Chemical Society, explores the latest advances in nano-DDS and their potential advantages compared with traditional drug delivery systems

The field of nanotechnology has experienced tremendous growth during the past few decades. This technology has gained momentum throughout many sectors, with applications in engineering, food/agriculture and beyond.

One of the most significant impacts of nanotechnology has been in the medical field. This trend is reflected in data from the CAS Content Collection, the largest human-curated collection of published scientific knowledge.

Biomedical applications have driven a significant amount of growth in the use of nanomaterials, with more than 50,000 scientific publications (including journal articles and patents) related to nano-DDS during the last 20 years.

Nano-DDS research is an exciting area of investigation, as these small but mighty particles promise to maximise the therapeutic benefits of drugs while minimising their adverse effects through bioavailability enhancement.

The challenges of drug delivery and traditional systems

Traditional methods of drug delivery include oral ingestion and intravascular (IV) injection. Although they are the mainstay of many treatments, there are limitations to these systems.

For example, traditional DDS result in only a small portion of the drug reaching the intended organs and non-targeted organs being affected.¹ This increases their toxicity and induces side-effects that result in poor patient experience and low medication adherence.¹

Toxicity is a particular issue within chemotherapies, with treatments commonly affecting healthy tissue and causing adverse effects.²

Neurological conditions such as brain tumours pose further challenges to DDS because treatment needs to be able to cross the blood-brain barrier (BBB).

The BBB excludes all large-molecule therapeutics — and more than 98% of small-molecule therapeutics — making successful treatments an urgent unmet need.³ In addition, DDS can suffer from low solubility, low bioavailability, low efficacy and rapid excretion.¹

To combat these challenges, scientists have been developing nano-DDS, which are proving to be successful and beneficial to patients.²

Understanding the key nano-DDS types 

Nano-DDS encompass a diverse array of innovative technologies that hav been designed to enhance the efficacy and safety of therapeutic treatments. These systems can be broadly classified into four categories based on their composition and structure: polymeric, inorganic, lipid-based and biological (Figure 1).

• Polymeric nano-DDS are currently the most popular class of nanoparticles in drug delivery, accounting for 32% of documents in the nano-DDS dataset in the CAS Content Collection. These nanoparticles can be customised with specific physical characteristics, encapsulating agents and surface attachments, allowing for the precise targeting of drugs to their intended destinations in the body.⁴
• Inorganic nano-DDS use materials such as metals, silica, calcium phosphate and others, offering diverse options to tailor DDS to specific needs. Metallic nanoparticles, in particular, offer advantages owing to their dense surface functionalisation potential and suitability for optical or thermal-based therapeutic and diagnostic techniques.⁵
• Lipid-based nanoparticles, like polymeric nano-DDS, are widely utilised, constituting nearly a quarter (24%) of publications in the CAS Content Collection.⁶ Lipid-based nanoparticles are superior to other nano-DDS in terms of minimising toxicity while maintaining solubility.⁷
• Biological nano-DDS, such as exosomes, are important mediators of intercellular communications and offer superior innate stability, low immunogenicity, biocompatibility and high capacity for membrane penetration.⁸

Collectively these technologies have widespread applications in cancer, haematology, immunology and other diseases, advancing methods of DDS and overcoming challenges faced by traditional systems.

Figure 1: Types of nano drug delivery systems (DSS)

The advantages of nano-DDS 

Enhanced drug delivery: As a result of specific engineering, nanocarriers can target drug delivery to specific cells, tissues or organs, helping to minimise drug-induced damage to healthy tissue.⁹

For example, nano-DDS can be used to target cancer cells, protecting healthy ones from the damage that’s often associated with chemotherapy, and reducing side-effects and drug resistance.^9,10

Nanocarriers are suitable for a wide range of therapeutic applications as they offer effective drug loading and release.¹¹ Nano-DDS also make simultaneous multiple drug delivery possible, benefiting patients undergoing combination therapies.¹⁰

Epidermal growth factor receptor (EGFR)-targeted polymer-blend nanocarriers loaded with paclitaxel and lonidamine have been developed to treat breast cancer … and they have demonstrated efficient loading and sustained drug release, resulting in improved combination therapy.¹²

Nanocarriers can also enhance drug performance, protect them from degradation or elimination before reaching the target site and reduce systemic toxicity.^10,13

For instance, gene-based therapies benefit from nano-DDS by allowing nucleic acids to cross the cellular membrane and avoid degradation.¹⁴

Improved therapeutic outcomes: Drug nanoparticles have a large surface area to volume ratio, which results in increased solubility and enhanced bioavailability. These qualities allow pharmaceutical companies to repurpose medicines that showed promising efficacy but were withdrawn from the development pipeline because of poor bioavailability. 

These same properties can also be tailored to optimise pharmacokinetics, thereby improving drug distribution, absorption and elimination.^2,9

In dermatology, for example, nanoemulsions can improve the topical delivery of treatments by increasing the contact surface area and controlling drug release, resulting in increased efficacy and bioavailability.¹⁵

The small particle size of nano-DDS also allows them to overcome biological barriers such as the BBB.³ Polymer-based nanoparticles, biomimetic-based nanoparticles and inorganic-based nanoparticles are all able to cross the BBB; this may have tremendous applications in historically hard-to-treat neurological diseases and brain cancers.³

Nano-sized carriers can also combine diagnostic and therapeutic (theranostic) functions, providing live updates on treatment efficacy.¹⁶ 

Enhanced patient experience: The use of more targeted drug delivery reduces toxicity and side-effects by avoiding drug exposure in healthy tissues and allowing the use of lower doses.²

DNA nanotechnology is a form of DDS currently under development that benefits from the self-assembly of nanostructures and molecules to improve drug targeting (with the aim of reducing toxicity).²

Nanocarriers can also prolong the circulation time, allowing for sustained drug release, which reduces administration frequency and results in improved patient compliance.¹³

For example, long-acting injectables of nanoparticle antiretroviral drugs represent the most advanced therapy for the HIV virus, improving both target bioavailability and patient adherence compared with previous therapies.¹⁷

In addition, nano-sized DDS can be personalised based on diagnostic information, resulting in more effective and individualised therapy.¹⁶

Summary

Nanotechnology is emerging as a prominent force in many fields, such as food, engineering and medicine … and a particular area of interest in nanomedicine is DDS.

Traditional DDS, the current mainstay of many treatments, suffers from limitations in terms of drug targeting, bioavailability, toxicity and efficacy. In contrast, nano-DDS offer more precise drug targeting, thereby reducing toxicity and exposure in healthy tissue.

These qualities, plus effective drug loading and release, all contribute to enhanced drug delivery, improved therapeutic outcomes and enhanced patient experience.

A broad range of nano-DDS are already in use and more are being developed, each with their own unique properties that have been designed to overcome the challenges of traditional DDS.

Nano-DDS bring their own challenges, such as manufacturing, regulation, cost and scale considerations, clinical translation, biocompatibility, biodistribution variability, and long-term safety concerns.

However, despite these challenges, nano-DDS holds incredible potential to change the treatment landscape and it’s an innovative solution to many treatment limitations faced by clinicians and their patients. 

References

1. https://www.jpsr.pharmainfo.in/Documents/Volumes/vol12issue04/jpsr12042005.pdf.
2. https://pubmed.ncbi.nlm.nih.gov/37764400/
3. https://pubmed.ncbi.nlm.nih.gov/33093794/.
4. https://pubmed.ncbi.nlm.nih.gov/36986636/.
5. https://pubmed.ncbi.nlm.nih.gov/30197553/.
6. https://pubmed.ncbi.nlm.nih.gov/37560754/.
7. https://pubmed.ncbi.nlm.nih.gov/34181394/.
8. https://pubmed.ncbi.nlm.nih.gov/36354238/.
9. https://pubmed.ncbi.nlm.nih.gov/29379334/.
10. https://pubmed.ncbi.nlm.nih.gov/30347840/.
11. https://pubmed.ncbi.nlm.nih.gov/36015192/.
12. https://pubmed.ncbi.nlm.nih.gov/20942457/.
13. https://pubmed.ncbi.nlm.nih.gov/29042776/.
14. https://pubmed.ncbi.nlm.nih.gov/34445243/.
15. https://pubmed.ncbi.nlm.nih.gov/29766488/.
16. https://pubmed.ncbi.nlm.nih.gov/22728642/.
17. https://pubmed.ncbi.nlm.nih.gov/33753915/.