In 1974, Dr. Robert Langer was part of the first cohort of researchers to begin nanoparticle research, as his lab at Cornell University developed tiny particles to deliver large molecules for angiogenesis. Since then, the field of nanomedicine has steadily progressed to reach high points such as the successful use of nanotechnology to deliver messenger RNA (mRNA)-based Covid-19 vaccines. Langer, now a David H. Koch Institute Professor at the Massachusetts Institute of Technology, and a shareholder, says 鈥淸Nanotechnology research] been steadily growing, but I think the success of the Covid-19 vaccines, which rely on nanoparticles, has accelerated it too鈥�.
Langer explains that nanoparticles can vary massively in formulation based on their uses. Researchers may develop nanodrugs due to their smaller surface area to allows drugs to dissolve faster, or nanoparticles may encapsulate drugs, so they last longer in the body. In the case of most mRNA vaccines, a lipid nanoparticle-based approach was chosen due to its ability to protect the mRNA in the body and prevent degradation. Covid-19 vaccines from Moderna and /BioNTech, which use lipid nanoparticles, became the only two FDA-approved vaccines for almost all ages.
Lipid nanoparticles are spherical vehicles made from ionizable lipids. They are positively charged at low pH and become neutral within the body, reducing their toxicity. Due to their size, cells can absorb them where they release products.
Olivier Jarry, CFO of the Spanish biotech Libera Bio, says there has been a shift in the industry following the success of the Covid-19 vaccines. 鈥淏efore this, people would say nanotechnology is not going to work well. Now with this example, I think they鈥檝e seen it work extremely well, so this is a ringing endorsement that nanotechnology can make a big difference鈥�.
In an email to this news service, Jo茫o Conde, PhD, professor at NOVA Medical School, Universidade NOVA de Lisboa, said advances like the mRNA vaccines serve as a testament to the breakthroughs made by science over decades of research at the junction of genetics and nanomedicine. 鈥淭his intersection will be remembered as one of the most significant achievements in science and medicine鈥�.
A journey within nanomedicine
Most of the initial research into nanomedicine focused on enzyme replacement therapy in the liver for enzymes such as , says Moein Moghimi, PhD, professor of Pharmaceutics and Nanomedicine, Newcastle University, Newcastle upon Tyne. With early nanoparticle studies, researchers often found the to drugs and the short-lasting effects of drugs challenging, as they can also reduce a drug鈥檚 efficacy. However, after a period of slow movement in the field, the FDA approved the first nanodrug, Doxil, for Kaposi sarcoma in 1995. Since then, the drug has been used off-label in breast cancer and other types of cancer.
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By GlobalDataHowever, following an initial buzz of activity in the field and excitement surrounding the approval, Moghimi says 鈥渢hings took a nosedive for a few years鈥�. The next wave came from early research into liposomes and lipid nanoparticles, both of which are used for drug delivery. He says, 鈥淚t gave a new lease [on] life to the field鈥�. Liposomes have the same function as lipid nanoparticles in drug delivery but have a simpler formulation. Liposome research paved the way for the design of current lipid nanoparticles.
Lipid nanoparticle drug delivery was in the spotlight during the Covid-19 pandemic. Moderna鈥檚 Spikevax and Pfizer BioNTech鈥檚 Comirnaty vaccines use lipid nanoparticles to encase the nucleic acids in the mRNA vaccine. Langer鈥檚 engineering lab was instrumental in the development of these lipid nanoparticles, playing into his role in co-founding Moderna. These vaccines have proven to be blockbusters, with Moderna earning $18.4 billion in Spikevax sales in 2022, and $37 million for Pfizer in 2022. GlobalData predicts that Comirnaty鈥檚 sales will increase by more than 20% between 2024 and 2027.
GlobalData is the parent company of 色界吧 Technology.
Using nanomedicine to overcome drug delivery barriers
Apart from lipid nanoparticles, nanoparticle-related innovation is also reaching other types of drug development. Conde says the use of has become more common over recent years. 鈥淣anoparticles can be tailored to target specific cells or tissues, release gene therapies in a regulated manner, reduce toxicity, and increase stability,鈥� he added.
Moghimi鈥檚 lab is also developing nanoparticle drug systems to help drugs cross the blood-brain barrier, a feat that has not yet been achieved. If successful, such applications could be used for neurodegenerative conditions like Alzheimer鈥檚 disease.
, developed by the company鈥檚 cofounder MJ Alonso, PhD, professor, Department for Pharmacy and 色界吧 Technology, Universidade de Santiago de Compostela, to deliver antibodies. Unlike mRNA vaccines, a lipid nanoparticle approach cannot be used for delivering antibodies as they vary too much in size and have both hydrophobic and hydrophilic areas, says Jarry. Thus, Jarry explains that Libera is developing multifunctional polymeric nanocapsules (MNPs) that use a lipid, an aqueous medium, and polymer nanoparticles. This design protects antibodies from the innate immune system. The outer layer of the carrier can have ligands added to it so it can target specific cells. He adds that this structure can deliver a small molecule inside the lipid phase and an antibody inside the aqueous phase.
鈥淔or diseases that are based on cell dysfunction, 75% [of targets] may be inside the cell and 25% on the cell surface. And the issue is that antibodies are too big to go directly inside the cell,鈥� he says. He also says this is great for drugs like Opdivo (nivolumab) and Keytruda (pembrolizumab), which target cell surface receptors, but it is difficult to select a range of other targets to treat diseases. Jarry expects to take the MNPs into the clinic in two years. 鈥淲e want this product to go to clinic, but we are more into designing the nanocarrier right now, so the sooner a big pharma takes them [the nanocarriers] for further development, the better,鈥� he says.
Langer鈥檚 lab is working on a range of drug delivery systems at the nanoscale level that can encapsulate nutrients for the developing world, or develop 鈥渟elf-boosting vaccines鈥� and more. He describes self-boosting vaccines as those that deliver an immunogen at set times. While still in preclinical studies, Langer鈥檚 lab is also investigating oral pills with an effect that can last longer than one week.
Still, several established challenges remain. 鈥淟ipid nanoparticles are one of the most promising delivery vehicles for nucleic acid-based therapies, but their production and utilization are fraught with difficulties. Stability, scalability, immunogenicity, targeting, and cost-effectiveness are issues,鈥� Conde says. 鈥淚t takes a long time to develop these types of formulations, because they’re very complex multicomponent [drug delivery systems] that are totally different from standard drugs,鈥� Moghimi adds.
Despite these problems, Moghimi predicts that nanoparticles will continue to make an impact in the future, especially lipid nanoparticles. 鈥淭here are still possibilities that these types of nanoparticles could be used for a whole range of nucleic acid medicines, whether mRNA, DNA, or CRISPR Cas9鈥� for different genetic diseases. These could feature in the next four to five years. Having these types of formulations would help the field of nucleic acids flourish,鈥� he says.
