Nanomedicine and drug delivery systems are at the forefront of modern healthcare. These systems offer a new platform for drug delivery that can greatly increase the targeting and effectiveness of therapy.
Over the last twenty years, great strides have been made in cancer nanomedicine and tissue repair using targeted drug delivery systems. In this field, the goal is to take advantage of the unique properties of a material on the nanoscale to minimize toxicity in healthy organs by specifically targeting cancerous cells. Our research group has sought to develop safer and more efficacious therapies in order to advance patient care and clinical outcomes.
Concerning nanomedicine, the focus of our research has been to improve the treatment of different types of cancer, among them lymphoma and glioma. We have developed polymeric and lipid nanoparticles loaded with different antitumor agents, such as edelfosine, which presents the singular characteristic of not targeting the cell’s DNA but the cell membrane and the apoptotic machinery of the cancer cell. These nanosystems were able to cross the blood-brain barrier, and furthermore, in the case of lymphoma models, they were found to successfully inhibit not only the primary tumor, but also its spread to other parts of the body when administered orally.
More recently, our attention has been centered on the use of nanotechnology for the treatment of pediatric cancers, particularly osteosarcoma, which is the most frequently observed primary malignant bone tumor in the pediatric population. We have shown that our nanomedicines decreased the toxicity of the entrapped edelfosine, and that this treatment slowed the progression of the primary tumor growth in orthotopic osteosarocoma animal models, successfully preventing the metastatic spread of the osteosarcoma cells from the primary tumor to the lungs — these findings were significant as it is assumed that 80% of patients with osteosarcoma present non-detectable micrometastases at diagnosis. The nanomedicines we have developed, and more specifically lipid based nanosystems entrapping edelfosine, could provide a more effective and safer alternative to conventional treatments for different types of cancers.
Regenerative medicine has also been of great interest to us. It is an interdisciplinary field that promotes regeneration of tissue or organs damaged by disease, which contrasts with traditional strategies that focus primarily on treating symptoms. In this sense, our focus has been the development of novel drug delivery systems to provide better treatment for brain and cardiac diseases. A large number of the projects carried out by our group have been done in collaboration with clinicians, pharmaceutical scientists, material engineers, and veterinarians, leading to novel delivery systems in key areas of unmet medical needs such as Parkinson’s disease and myocardial infarction.
Specifically, our biomaterials can solve one of the greatest issues associated with biotherapeutic formulation and delivery, which is their fast degradation. In order to overcome this challenge, we have designed various microparticle-based technologies which we are able to protect biomolecules from degradation in biological environments. Our technique avoids shear stress and preserves the proteins from degradation during the manufacture process.
We have demonstrated that the injection of microparticles loaded with glial cell line-derived neurotrophic factor (GDNF) — one of the most promising candidates for the treatment of Parkinson’s disease — within the brain of animals with severe nigrostriatal degeneration achieved long-term improvement in motor function, which was associated with the restoration of the dopaminergic function.
Similar to the positive results observed in the treatment of Parkinson’s disease, we also observed improved cardiac recovery after myocardial infarction after treatment with neuregulin or fibroblast growth factor loaded microparticles. Interestingly, these microparticles modulated the inflammatory process towards a reparative response. However, we are only starting to obtain a glimpse into the crucial role of the inflammatory response for tissue repair. More studies addressing the contribution of different macrophage subsets to the reparative process are mandatory to fully understand the therapeutic potential of modulating the inflammatory response, as therapeutic treatment not only for myocardial infarction, but also for several other diseases, including cancer.
Beyond assessing the efficacy of microencapsulated biotherapeutics, microparticle optimization has also been a regular topic of discussion in the research group. The hydrophilic polymer coating, poly (ethylene glycol) (PEG), is well-known to increase the half-life of biotherapeutics and to reduce particle clearance in the blood, but the same strategy has not proven effective in reducing particle elimination in the heart. PEG decreases particle clearance in the blood by blocking opsonins, macromolecules that bind particles and mark them to be eliminated by phagocytes. However, in the cardiac tissue, particle clearance may not be dependent on opsonins – which would explain why PEG failed to improve microparticle bioavailability in the heart.
Mirco- and nanoparticle-based drug delivery systems combined with cell therapy can achieve a more complete and potent regenerative response. Indeed, biomimetic biomaterials with tunable properties can be tailored to influence the fate of transplanted cells and to improve current cell delivery strategies. Within this framework, the use of microparticles as delivery vehicles for stem cells and human cardiomyocytes has proven to maximize the efficacy of cell therapy by dramatically enhancing cell survival in the heart. Cutting-edge areas such as non-invasive intravenous delivery of cardioprotective nanomedicines or extracellular vesicle-based therapies are also currently being explored.
Despite increased efforts made to improve current strategies in the above mentioned diseases, there are still aspects that limit the transfer of drug delivery systems to clinical practice, including the standardization of criteria and validated methods to characterize these novel systems of drug administration, large scale-manufacturing, the use of animal models that better simulate the pathophysiological aspects of the diseases and government regulations. An additional issue that could influence their clinical translation is the overall cost-effectiveness in comparison to current therapies.
In any case it is clear that the advances achieved in nanomedicine and drug delivery technologies offer huge potential for novel therapeutic approaches to unmet medical needs such as cancer, as well as cardiovascular and neurodegenerative diseases.
Written by: María Blanco-Prieto [1]
[1] Department of Pharmacy and Pharmaceutical Technology, Universidad de Navarra
Reference: Elisa Garbayo, et al. ‘Nanomedicine and drug delivery systems in cancer and regenerative medicine.’ WIREs Nanomedicine and Nanobiotechnology (2020). DOI: 10.1002/wnan.1637
