Drug Delivery Blog: Nanotechnology-based drug delivery systems

Nanotechnology-based drug delivery systems hold tremendous potential

One of the most important challenges in drug development is efficient delivery of the drug molecule to the appropriate tissue to drive therapeutic benefit, while minimising side effects. For small-molecule drugs, a suboptimal ‘therapeutic index’ between the doses that deliver desired and undesired effects can limit effectiveness or even halt progression through clinical trials. For non-small-molecule drugs, such as antibody-drug conjugates and oligonucleotides, their high molecular weight and other properties can limit their distribution throughout the body, thereby preventing the drug from reaching its target and exerting a therapeutic effect.

The challenge

Imagine an anti-cancer drug designed to kill a tumour. When given to the patient, this drug molecule needs to move through the circulatory system, navigate the extracellular environment, penetrate the tumour tissue before it gets removed and metabolised and finally enter the cell and bind to its target. All while causing minimum effect on normal cells.

The solution

Nanotechnology-based drug delivery systems hold tremendous potential to overcome these challenges. Designed to carry the drug(s) or genes specifically to the target cells or tissues, the systems release it at the desired concentrations, decreasing undesired toxicity effects. This allows for rapid evaluation of treatment efficacy in the early stages.

Over the last decade, dozens of nanomedicines have received clinical approval, with many more in preclinical development or in clinical trials.

Critical questions

For nanomedicines to be successful in the clinic, an in-depth mechanistic understanding of these delivery systems is crucial. There are several critical questions that need answers:

• How do they enter the cell?
• Once they have entered the cell, which cellular compartments do they go to?
• Are they trapped in a specific compartment and degraded?
• Do the cells throw them out before they release their cargo?
• Do they release their cargo at an effective concentration?

Answering these questions will help to develop an effective drug delivery system. Once the delivery mechanism is understood, the properties of the system (size, surface charge, shape, hydrophobicity, surface chemistry) can be tailored to evade biological barriers and achieve optimal cellular uptake across different organ systems to treat various diseases.

Cellular entry and trafficking of nanomedicines

At Medicines Discovery Catapult, we have developed a microscopy-based platform to study the cellular entry and trafficking of nanomedicines. This image-based platform provides a sensitive and robust method for evaluating nanomedicines in cellular systems and enables further improvement of drug delivery systems.