The promising organ-on-chip/nanotech combination

L’abbinamento tra due delle innovazioni più interessanti nell'ambito della ricerca farmaceutica potrebbe fornire un ulteriore impulso allo sviluppo di farmaci più efficaci e sicuri

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Biomaterials in organ-on-chip technology, representing the future of drug testing

Nanotechnology and organ-on-chip platforms represent two of the most promising innovations in pharmaceutical research and new drug development, offering significant advantages in therapeutic precision and reliability of preclinical testing.

Nanotechnology in drug delivery

Nanotechnologies applied to drug delivery enable the creation of extremely sophisticated drug delivery systems and promise to revolutionize therapeutic efficacy and drug safety. According to a recent review, nanoparticles improve the solubility, stability and bioavailability of drugs, especially hydrophobic drugs.

In addition, the ability to modify the surface of nanoparticles makes it possible to develop delivery systems that can target specific cells, tissues, or organs, improving the precision and efficiency of treatments. It is precisely the ability to tailor nanoparticles to specific circumstances that enables a more targeted and personalized approach to disease treatment. This makes it possible to adapt therapies to individual patient characteristics, improving efficacy and reducing side effects.

More precise and safer drugs

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One of the best-known examples of use in nanotech is mRNA vaccines, such as those developed by Pfizer-BioNTech and Moderna for Covid-19, which use lipid nanoparticles (LNPs) to transport mRNA to cells, where it is translated into antigen to stimulate an immune response. Another well-known application is paclitaxel, a chemotherapeutic used in the treatment of metastatic breast cancer, combined with albumin to form nanoparticles that improve drug solubility and reduce hypersensitivity reactions. This approach led to a significant reduction in side effects associated with the treatment.

Currently, as part of the project Tuscany Health Ecosystem (THE), one of eleven innovation ecosystems funded by Mission 4 (education and research) of the National Recovery and Resilience Plan (PNRR), smart nanoparticles are being developed that can cross physiological barriers and release drugs only in the target tissue.

In particular, the most promising ones turn out to be lipid nanoparticles, made by advanced microfluidic techniques, which, being composed of the same lipids as cell membranes, provide excellent biocompatibility and high stability. Thanks to these technologies, therapeutic precision increases significantly, enabling treatment of neurological and oncological diseases hitherto difficult to address by traditional methods, reducing drug waste and improving patients’ quality of life.

Organ-on-chip

In parallel, organ-on-chip platforms are emerging as a promising alternative to traditional animal models used in preclinical research. These microfluidic devices contain live human cells arranged in three-dimensional structures that simulate organ functions.

Microfluidic devices are miniaturized systems designed to manipulate and control small amounts of fluids (usually at the microliter or nanoliter scale) within micrometer-sized channels and chambers. These devices make it possible to create highly controlled environments, useful for reproducing physiological conditions and studying biological and chemical processes with high precision and reproducibility.

Several on-chip models have been developed, e.g., those of kidney, brain, eye, bone, and reproductive organs that allow more precise study of drug interactions and physiological responses than traditional two-dimensional cell cultures.

The multi-organ, evolution of the on-chip

An evolution of this technology is the multi-organ systems designed to replicate human physiological conditions of several organs simultaneously allowing the study of inter-organ communication and the processes of absorption, distribution, metabolism and excretion of drug candidates with more precision due to the possibility of investigating the off-target toxicity of drugs and their metabolites.

However, despite the many promising developments in the field of organ-on-a-chip, limitations still exist related to the complex cultivation procedures required to create and maintain the various organ models. Moderate throughput hinders the transition from academic circles to the industrial sector.

Recent studies have also validated the combined effectiveness of nanotechnology and organ-on-chip platforms in drug research. In particular, the integration of these technologies would allow for an acceleration of the pharmaceutical development process and a significant reduction in the costs associated with the initial stages of clinical trials although, a research paper published in “Nano Convergence” explains, studies are only in their infancy and “significant progress” still needs to be made in adapting the design and capabilities of organ-on-chips to the specific needs in the field of nanomedicine.”

However, with the rapid increase in research interests in this area, it is not difficult to predict that organ-on-a-chip technology will play an instrumental role in the development of nanotherapeutics in the future. “As in vitro platforms with unprecedented predictive ability,organ-on-a-chip are capable of making a great contribution to the advancement of the nanomedicine frontier.”