Author: Lois Ng
Editor: Helen Wu
Are you a fan of the Marvel, Terminator, or Star Trek series? If you are, you have probably heard of nanotechnology. Significant progress has been made with nanotechnology in recent decades, including carbon nanotubes for electronics, nanoscale eyeglass films for water resistance, and, of course, the infamous Iron Man lightweight body armour. Nanotechnology has major implications for disease prevention, diagnosis, and treatment in medicine. In this article, we delve into the biology behind common nanomedicines, clinical applications, and the challenges involved.
The history of liposomal nanotherapeutic drugs
Since the 1990s, drug delivery targeting specific cells has largely relied on nanomedicine. Being of small size (10 nm–100 nm), nanotherapeutics are shown to have increased precision and reduced side effects by non-specific drug toxicity. After the discovery of the liposome structure in 1964, the first nanotherapeutic was approved, named doxorubicin (Doxil) by the FDA. Liposomes have an outer lipid membrane surrounding an inner aqueous core, where soluble drugs can be loaded, allowing the protection of healthy tissues from drug toxicity. Often used in combination with chemotherapy, doxorubicin targets and disrupts DNA synthesis in target cells, leading to cell death. Other forms of nanotherapeutics have since been used, including polymer-based nanocrystals, protein-based drugs, and inorganic drugs.
Other forms of nanomedicines
Polymer-based nanomedicines involve the conjugation of drugs to polymers, increasing drug solubility and circulation time. With a hydrophilic surface and hydrophobic centre, non-water-soluble drugs can be loaded into the core in drug delivery. Genexol-PM is a polymeric form of the less soluble drug paclitaxel for the clinical treatment of breast and non-small cell lung cancer in South Korea. However, the clinical use of these drugs is limited due to the slow biodegradation of the polymer backbones, leading to low drug release rates. Current research is being done on using exogenous or endogenous stimuli to trigger controlled drug release on target tissues.
Clinical applications
65% of current trials in nanotherapeutics are focused on cancer medicines, providing early diagnosis and targeted treatments. The main goal of nanomedicines in cancer research is to improve the quality of life of patients using drug delivery systems and immunotherapies. The ability to locally deliver drugs and apply nucleic-based immunotherapies can significantly reduce side effects and ensure therapeutic outcomes.
Furthermore, certain nanomedicines are able to pass through the blood-brain barrier through transcytosis, delivering therapeutic agents to the central nervous system. Applicable results are shown in preclinical trials in animal models, tailored to treat neurological disorders such as Alzheimer’s disease, Huntington’s disease, and gliomas, allowing ongoing research on the role of nanoparticles in the treatment of neurodegenerative diseases. Other uses include imaging with iron oxides, which lowers the number of doses of diagnostic compounds; wound and antibacterial treatments with gold nanoparticles and quantum dots; tissue engineering; and nanosensors, which monitor intracellular glucose levels and pH, allowing detection of cell abnormalities and prevention of diseases.
Challenges
One of the main challenges in drug delivery is the solubility and permeability of hydrophobic drugs. Nanocrystals increase oral bioavailability due to enhanced surface area and drug saturation solubility, allowing fast dissolution rates, especially when absorbing hydrophobic drugs that have a low solubility in water. They are pure drug crystals with dimensions of <1 um, and carrier systems are not needed. Due to their mucoadhesive properties, nanocrystal drugs have increased residency in the mucosa of the gastrointestinal tract where they are absorbed, maintaining a high concentration when released. Therefore, they can be delivered in the form of drug tablets, capsules, intravenous, or intra-nasal delivery, allowing a wider range of dosage options and avoiding the side effects of nanocarriers. Despite the high reproducibility of nanocrystal drugs, their production requires high energy input, leading to high production costs. Furthermore, the process lacks a controlled mechanism for drug release with fast dissolution rates, making it unsuitable for cytotoxic drugs as a targeted medicine.
The increasing global commercialisation of nanomedicines, particularly in North America and Europe, brings biological challenges such as biodistributions, large-scale reproducibility, cost, and safety concerns regarding the toxicity of certain nanocoatings and ligands. More importantly, there is a lack of appropriate methods for characterising nanoparticles, safety, and quality reference standards for nanomedicines, including size parameters and aggregation states. In addition, both traditional drugs and certain nanomedicines are often unable to balance between destroying infected tissues and maintaining healthy ones. Smart nanotherapeutics, like Thermodox (heat-sensitive liposomal doxorubicin), are addressing this gap by actively targeting infected tissues through stimuli like endogenous temperature or pH changes, thereby enhancing clinical precision and cell efficacy.
Nanotechnology has been crucial in the clinical development of drugs with a wide range of solubility profiles. It also has big effects on areas like vaccine development, imaging systems, and drug delivery. However, certain nanotherapeutics require further research due to their lack of concrete structure-function relationships and reproducibility. Pharmaceutical research on nanomedicines is the focus of research efforts, leading to the discovery of new treatments with increased efficacy and precision to target pathogenic cells.
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