A recent review published in the
Journal of Nanoparticle Research discusses the engineering versatility of polymeric nanoparticles – making a good therapeutic alternative against coronavirus diseases.
Study: Polymeric nanoparticles as therapeutic agents against coronavirus disease. Image Credit: Billion Photos/Shutterstock Nanotechnology and SARS-CoV-2
New and breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), have reduced the efficacy of the vaccines developed against the virus. With an impending increase of infections in many countries, despite the mitigating strategies that have been ongoing for the past couple of years, there is yet no approved cure or novel treatment for the SARS-CoV-2 infection and its progression into COVID-19.
This has established the urgency for alternative therapeutic solutions. The ongoing COVID-19 pandemic and the possibility of future outbreaks spell out challenges on several fronts to overcome with minimal harm and affliction. Nanotechnology is the welcome technology that can enable us to combat infectious diseases and other medical complications.
Researchers review the possibility and latest advancements of polymeric nanoparticles as therapeutic agents against coronavirus in this context.
Characteristics of polymeric nanoparticles
These are colloidal particles, ranging in size from 10-999 nm, and composed of natural or synthetic polymers, such as chitosan and polypeptides, respectively, or even pseudosynthetic single polymer chains or larger chain aggregates.
Due to the inherent colloidal stability and the tunable surface functionalities, these nanoparticles have characteristics such as:
can be used for easy targeting,
reduce non-specific binding,
reduce adverse effects and avoid undesirable interactions with the immune system,
also extend their circulation in the bloodstream,
protect therapeutic agents from degradation, increasing the stability, bioavailability, and pharmacokinetics of drugs,
ease of chemical modification, and
ability for controlled drug release.
These unique physical-chemical characteristics improve the therapeutic effects of the polymeric nanoparticles.
On the other hand, the nanoparticles can also be engineered to interact with the immune system as an adjuvant or a cargo carrier in vaccines. Because these polymeric nanoparticles are easy to engineer, they provide high versatility, which enables one to have (i) specificity, (ii) tunable release kinetics, and (iii) multimodal drug composition. Thus, these features overcome the common limitations encountered in traditional drug development.
Consequently, polymeric nanoparticles are among the top Food and Drug Administration (FDA)-approved nanodrugs; they are used to treat cancer, bone regeneration, and autoimmune diseases.
Two extremely advantageous polymers that are also FDA-approved are Polylactide (PLA) and Poly Lactic-co-Glycolic Acid (PLGA). These are synthesized using nanoprecipitation and emulsification processes – the parameters of which minutely craft the properties of the polymeric nanoparticles such as shape, size and size distribution, surface charge, and stability. These determine the therapeutic utility of the nanoparticles.
The reviewers discuss the processes, emphasizing the importance of functionalization (i.e., vectorization, immobilization, or bioconjugation) or loading with different bioactive compounds. For example, the antiviral drug Veklury (remdesivir) may be tested by encapsulating it in polymeric nanoparticles (lisinopril-capped remdesivir-loaded PLGA nanoparticles). The loading of the drug onto the nanoparticles can be done after the preparation of the nanocarriers or the desired chemical moiety inserted during the polymerization of the nanoparticles (
in situ functionalization).
The polymeric nanoparticles loaded with the drug may be used through two fundamental approaches: passive targeting (such as in the case of inflammation and hypoxia) and active targeting (escaping the reticuloendothelial system (RES) clearance).
PEGylation is the addition of polyethylene glycol (PEG, a non-immunogenic polymer) to the surface of the nanoparticle; a strategy used to avoid the RES system, improve the circulation time and therapeutic efficiency in the body. Poly(vinyl acetate) (PVA), with its low toxicity and high biocompatibility, is also one of the FDA-approved polymers used to stabilize nanoparticulate systems.
Polymer-based nanotechnology approaches
Of the strategies to prevent SARS-CoV-2 infection, one of the approaches in the nano-regime is to saturate the viral receptors with nanoparticles before the virus could attach and enter the host cell to replicate and infect. These nanoparticles functionalized with the angiotensin-converting enzyme 2 (ACE2, the viral Spike proteins' receptor) and CD147 proteins could saturate the SARS-CoV-2 receptors, thus reducing their availability and blocking viral entry into our cells.
Similarly, multifunctional alveolar macrophage (AM)-like nanoparticles have membranes with coronavirus receptors with internalized PLGA nanoparticles doped with a photothermal molecule – the virus binds to the nanoparticles before binding to the host cell membrane and is then photothermally deactivated.
The promising polymeric nanoparticles for COVID-19 disease and sequelae are PLGA NPs, chitosan, polyanhydride, poly-γ-glutamic acid, and N-(2-hydroxypropyl) methacrylamide/N-isopropyl acrylamide (HPMA/NIPAM), which are already developed and improved to be applied in cases of the influenza virus (H1N1), bovine parainfluenza 3 virus (BPI3V), swine influenza virus (H1N2), and respiratory syncytial virus (RSV).
Also, many drugs are loaded onto nanoparticles (gelatin, albumin, etc.) to treat asthma, tuberculosis, cancer, etc. These drugs could be modified and tested for use against the SARS-CoV-2, which causes respiratory distress, inflammatory hijack or cytokine storm, cough, and fever – clinical manifestations paralleling other diseases.
Thus, polymeric nanoparticles are excellent systems for encapsulating antivirals and potentially inhibiting infections, with improved bioavailability, controlled release, and reduced side effects.
In the context of vaccines, the current COVID-19 vaccines are composed of cationic lipid nanoparticles. These polymeric nanoparticles are excellent robust systems for genetic materials and other immunomodulatory compounds for vaccination.
Importantly, the polymeric nanoparticles are compatible with hydrophilic and hydrophobic drugs, with simple and suitable preparation methods that achieve the required polymer-length, nanoparticle size, desired administration route, and the drug carried.
In the current pandemic, the polymeric nanoparticles are relevant systems with their specific applications in diagnostic sensors for detecting viral pathogens, physical barriers such as masks/shields to protect against viruses, and vaccines.
In addition to therapeutic applications, forefront in vitro technologies such as 3D bioprinting and organ-on-chip devices, used for accurate prediction of performance and safety of nanoparticles, are pivotal in approaches against COVID-19. These systems, including bioprinted tissue-like constructs on chips, are indispensable in investigating and assessing the nanoparticles' pharmacokinetics and dynamics, mimicking the physiological environment and responses.
In surmise, research and technology of polymeric nanoparticles against COVID-19 should be optimized with regulation, safety, and process manufacturing steps to achieve practical clinical applications.