Have any of you seen them? Used them? Contact with them? The answer is definitely yes because nanoparticles are everywhere around us.
Although, currently, there is a coexistence of different definitions of nanomaterials in the EU which causes discrepancies between some sectors, according to the European Commission recommendation issued in 2022, nanomaterials are natural, incidental, or manufactured material consisting of solid particles present, either on their own or as identifiable constituent particles in aggregates or agglomerates where 50% or more of these particles in the number-based size distribution fulfills at least one of the following conditions:
- one or more external dimensions of the particle are in the size range 1 nm to 100 nm,
- the particle has an elongated shape, such as a rod, fiber, or tube, where two external dimensions are smaller than 1 nm, and the other dimension is larger than 100 nm,
- the particle has a plate-like shape, with one external dimension smaller than 1 nm and the other dimensions larger than 100 nm.
Undetectable by the human eye, nanoparticles can exhibit significantly different physical and chemical properties to their larger counterparts.
To imagine nanosize, remember that the diameter of a human hair is 100 µm, a human cell is 10 µm. Bacteria are ~1 µm in size, but water molecule is ~0.1nm
Fig. 1 Size of nanoparticles
Researchers realized the importance of nanoparticles when they found that size can greatly influence the physiochemical properties of such substances.
Nanotechnology is helping to improve, even revolutionize, many technology and industry sectors, including information technology, homeland security, cosmetics, transportation, energy, food safety, environmental science, and medicine. The sector with the greatest potential for expansion and development over the next decade is nanomedicine.
As our knowledge of the human body continues to improve, nanotechnology opened a possibility to monitor, repair and control human biological systems at the molecular level, because offers unique opportunities for new therapeutic approaches to diagnose, prevent, treat and eradicate life-threatening diseases and conditions, such as cancer or diabetes, as well as resolving a chronic pain, which is a huge worldwide problem. Nanomedicine can improve many medical techniques, bone repair, or surgical operation techniques through highly advanced and targeted nanotechnological approaches.
The words nanomedicine, nanotechnology, nano-device are present in the public space, not just in the scientific one.
Are nanoparticles in your favorite beverages and food?
Let’s take a closer look at nanoparticles and their presence around us. Do you believe that 5 nm nanoparticles were found in the two most popular worldwide beverages, Coca-Cola and Pepsi? Now, all of us can probably say that nanoparticles are really everywhere, and we have daily contact with them.
So, despite the undisputed unique properties of nanomaterials, we cannot forget that nanomaterials not only impart critical advantages but also could cause toxicity because of their unwanted interactions with biological and cellular processes. The possible passage of nanomaterials into air, water, and soil ecosystems could result in diverse environmental impacts. Every day, in the public domain, we can read or hear about nanoplastic pollution, the detection of nanoplastics in wild organisms, and some aspects of the open debate on nanomaterial safety.
Many of us probably asked whether we have anything to fear?
No, because food safety in Europe is ensured by the European Food Safety Authority (EFSA). Recently, EFSA published a new approach to risk assessment, including a discussion of challenges, on how to assess the safety of nanoparticles in food [1].
EFSA recommends a detailed physicochemical characterization of nanomaterials, covering toxicodynamics and toxicokinetics. According to all EFSA regulations and recommendations, the focus during the assessment has to be on degradation/dissolution, genotoxicity, cytotoxicity, oxidative stress, and (pro-)inflammation characteristics.
Note, that some nanoparticles occur naturally in some foods, a good example is milk. Casein micelles in milk are protein nano-spheres, which are more available for us to absorb.
Ubiquitous additives in food are titanium dioxide, a whitening agent, or silicon dioxide, an anticaking agent; both usually contain microsize particles and nanoparticles.
Nanoparticles can quickly and easily reach taste buds on the tongue, so their level of use could be decreased. Nanoparticles might also extend food shelf life or reduce the need for added fats.
Summarizes, do not worry. EFSA watches and regulates requirements for food and feed products containing small particles, including nanoparticles.
Nanoparticles in medicine
Medical applications of nanoparticles
Let’s moved to the medical applications of nanoparticles.
The Nanotechnology Product Database currently contains 1318 products from 578 companies and 48 countries. Interestingly, the database divides a product into 6 categories: dentistry (90 products), disinfection (103 products), medical supplies (506 products), Pharmaceutics (432 products), Prosthesis and Orthopedy (26 products), and Tissue Engineering 61 products.[2]
The European Medicines Agency’s (EMA) published a scientific guidelines on nanomedicines, which help drug product developers prepare marketing authorisation applications for nano-human medicines. A complete list of scientific guidelines can be found here.
Moreover, for Marketing Authorization Applications (MAA) in Europe, the regulatory system allows the opportunity of “scientific counseling” from regulators to applicants, from the early stages of research and development.
Advancements in nanotechnology for drug delivery
A bit of knowledge of chemistry and physics will come in handy.
Every material’s properties change as its size approaches the atomic scale due to the increasing surface area to volume ratio. Nanoparticles’ very small size and very large surface area to volume ratio, compared to non-nano-size materials, are unique features of nanoparticles that cause unexpected optical, physical, and chemical properties.
Fig. 2 Various classes of nanotechnology-based materials for the medical application [3]
Nanoparticles are small enough to confine their electrons and produce quantum effects.
Over the last two decades, the Food and Drug Administration (FDA) and EMA have approved nearly 80 nanoparticle products.
Some of the last top use is lipid nanoparticles as a delivery system for nucleic acids, including mRNAs in Covid-19 vaccines, prepared by Pfizer, BioNtech, Moderna and Novavax [4,5]
The available nano-drugs demonstrated that they enhance active substance bioavailability, eliminate some side effects, and deeply increase the therapeutic effect overall.
Moreover, nanoparticles play a crucial role in solving one of the pharmaceutical industry’s huge challenges: the poor solubility of many active substances in water.
Nearly 40-50% of the valuable oral drugs marketed in the USA and Europe and almost 90% of the new chemical active substances in the drug development stage are poorly water-soluble.
Advanced single-step and multi-step nanoparticle production and isolation methodologies are being developed and used. RESS (Rapid Expansion of Supercritical Solutions), SAS (Supercritical antisolvent), SAS-WTS (Supercritical antisolvent process integrated with Wurster type coater), SAS-EM (Supercritical Antisolvent Precipitation with Enhanced Mass
transfer), SpEDS (Suspension-Enhanced Dispersion by Supercritical Fluid), SAS-DEM (Supercritical antisolvent – Drug Excipient Mixing), RESS-WTS (Rapid Expansion of Supercritical Solutions process in combination with the Wurster coater), RESS-BFB (Rapid Expansion of Supercritical Solutions process in combination with the Fluidised Bed), SAS-FB (Supercritical Antisolvent Precipitation with Fluidised Bed).
Fig. 3. Single-step and multi-step nanoparticle production and isolation methodologies [6].
Currently, for poorly soluble APIs, nano drug delivery systems and techniques open a new era for generating nanoproducts, which includes, e.g., canonization, complex or micelle formation, encapsulation, nanosuspension formation, supercritical fluid, high gravity precipitation, no precipitation techniques, nano gels, or nano matrices formation.
Old, well-recognized techniques, like spray drying and freeze drying, are also used, but in a new version.
Nano-based systems are also attractive for many other reasons, including their ability to protect APIs from degradation, both in storage and during transportation in the body.
Second, the nanoparticles can influence the distribution, manage where the drug accumulates in the body and how long it circulates before elimination,
Third, nanoparticles can change how the drug interacts with the cells at the target site.
Currently, the majority of approved therapeutic nanoparticles are in the EU market. The first nano-drug for cancer treatment was a PEGylated liposomal formulation of doxorubicin Doxil® and Caelyx®. Nowadays, Nanocrystal based drug product includes Rapamune® or Epaxal®, lipid base nanoparticles product includes DepoCyt®, Myocet®, Caelyx®, Nepact®, Onpatro®, Visudyne®, Inflexal®, Zevalin®, DepoDur®, AmBisome® or Vyxeos®.
Many drugs are in the pipeline, such as products based on soy phosphatidylcholine (SPC-3), cholesterol, dipalmitoyl phosphatidyl glycerol (DPPG), and methoxy-PEG-stearoyl phosphatidyl ethanolamine (mPEG2000-DSPE), chitosan, number of modified polymers, silica-based nanoparticles, metallic nanoparticles, carbon nanotubes, dendrimers or nanodiamonds.
Nanoparticles in regenerative medicine
A challenging interest of nanoparticles in medicine is regenerative therapy, which mainly focuses on designing new biocompatible materials that can enhance tissue repair and regeneration. Life expectancy is increasing, so there is increased interest in developing and directly administering therapeutic nanoparticles to promote bone regeneration. The most advanced used nano-delivery systems for bone regeneration are synthetic PLA or PLGA or natural polymers such as collagen, gelatin, albumin, and chitosan. Besides polymeric, various formulations of non-polymeric nanoparticles (silica-based, metallic) have also been used as nano-delivery systems for bone regeneration. Calcium phosphate-based non-polymeric nanoparticles are mostly used due to their similarities to human bone.
Micro/nanomotors for regenerative medicine are developing rapidly. Main design strategies include 3D-printing, microfluidic, biohybrid, and polymer template methods [7].
Soon, what is probably not easy to imagine for all of you, nanorobots can be one of the options for cancer treatments; many such vehicles made a way from theory to practice, from in vitro experiments to in vivo applications, so let’s ask are our society you able to accept such a treatment? [8]. A crucial aspect for EMA to register such a product will be explicit confirmation of the mechanisms of interactions between nanorobots and proteins/cells/tissues/organs and the proper and broad nanomaterials characterization with particular attention on biosafety and clear in vivo metabolic behavior.
Challenges and future potential of nanoparticles in medicine
Nano-based technology has made enormous progress over the last decades, currently, the huge numbers of products, not only medicines, that either contain or require nanoparticles for their manufacturing and functionality.
Nanotechnology offers many advantages in various fields of science and life. Many drug products on the market proved nanoparticle’s potential in many medical applications. Nanoparticles overcome some challenges associated with conventional therapy, however, some issues like side effects and toxicity are still discussed and unsolved. Despite their undoubted limitation, a high level of understanding, an advanced level of development and a huge range of different biological interaction testing definitely will achieve many strategies for the treatment, prevention, and diagnosis of many diseases, particularly those still untreatable ones.
SciencePharma experts offer support in designing development studies, pre-clinical and clinical trials, as well as preparing complete dossiers. We assist in innovative projects that have the potential to shape the future of medicine.
References
- https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2024.EN-8826
- https://product.statnano.com/industry/medicine
- Abid Haleem, Mohd Javaid, Ravi Pratap Singh, Shanay Rab, Rajiv Suman, Applications of nanotechnology in medical field: a brief review, Global Health Journal,7, 2,2023, https://doi.org/10.1016/j.glohj.2023.02.008. https://www.sciencedirect.com/science/article/pii/S2414644723000337
- https://www.sciencedirect.com/science/article/pii/S1773224722004646,
- https://pubs.rsc.org/en/content/articlepdf/2024/nr/d4nr00019f
- Vivek Verma, Kevin M. Ryan, Luis Padrela, Production and isolation of pharmaceutical drug nanoparticles, International Journal of Pharmaceutics,603,2021,https://doi.org/10.1016/j.ijpharm.2021.120708. https://www.sciencedirect.com/science/article/pii/S0378517321005135
- https://www.sciencedirect.com/science/article/pii/S2590049822000777
- Kong, X., Gao, P., Wang, J. et al. Advances of medical nanorobots for future cancer treatments. J Hematol Oncol 16, 74 (2023). https://doi.org/10.1186/s13045-023-01463-z