Mehdi’s Biomaterials Blog: Post 2
9/29/18
This week, we learned about nanoparticle drug delivery systems, as well as certain drawbacks and limitations scientists are facing in translating implement the vast research in clinical trials. A quick recap: nanoparticles are exciting because of their relatively huge surface area compared with microparticles or other bulk materials. Thus, while nanoparticles intrinsically don’t have any currently known novel properties, their formulations with other compounds and polymers hold great potential for drug delivery. Nanoparticle systems are created solely for the purpose of clinical use: the important factors that need to be considered are how a system reduces drug dosage, improves efficacy and safety, drug solubility, etc.
Within the field of drug delivery, targeted drug delivery to tumors holds the most intriguing place among the scientific community. The majority of drug delivery articles have been posted about this. This is because nanoparticles are intrinsically able to permeate and be retained inside the tumor microenvironment; likewise, their accumulation inside the tumor is vastly increased simply by increasing blood circulation time. However, recently there has been a general disappointment among the scientific community over the prospect of actively targeted drug delivery. This is because of the poor statistical efficiency of such drug delivery systems: less than 10% of the dose actually reaches the tumor, such systems are too dependent on passive permeation into tumor environments, and each system takes an unsustainably long and individualized time to create.
Thus, scientists have began to focus specifically on those biologically dynamic factors that every intravenously delivered nanoparticle system inherently depends on: the physical (temperature, light, magnetism, electricity), chemical (pH and ions), and biological (enzymes, antibodies, small molecules) components that nanoparticles drugs would encounter in the tumor microenvironment.
Enter: Smart Nanoparticles
Smart nanoparticles have been engineered to respond to factors such as ultrasound, light, and temperature. After delivery, UV or radiofrequency waves are used with high spatial and temporal resolution to enhance extravasation of drugs to the interstitial space. This has allowed various liposome and micelle formations to form chains and multivalently stick to tumors; alternatively, the nanosphere shell has been split open to fully release the drug to the entire volume of a tumor site. Further, using ultrasound for about 20min induces tumor vessels for maximum extravasation to nanoparticles; further heating results in very fast release of the drug from the nanoparticles.
However, these developments also come with limitations: a chain of specific events needs to happen for this highly efficient drug delivery, including precise temperature changes for example that are simply unrealistic in a large system such as the human body.
The article concludes by admitting that scientists have been complacent in their design of nanoparticle formulations. The current design is based on the passive EPR effect, even though most publications assert that the drug delivery through EPR is marginal at best. As a result, very few nanoparticle formulations have been translated to clinical trials, despite their potential. Mouse studies are simply too disconnected from clinical practice. This makes me recall Professor Gonzalez’s stress on human centered design. Perhaps the scientific community is approaching the study of nanoparticle delivery to tumors inefficiently by focusing on mouse models. For over two decades, the EPR effect has been considered the primary focus of drug delivery. Perhaps now it is time to examine the advantages of nanoparticle drug delivery systems with respect to the human body first.
