What are the latest drug delivery systems made of?
Polymer combs, gel cakes and hydrophobic tails… Professor Uchegbu and her team at Strathclyde University have been using water soluble biopolymers attached to hydrophobic chains to create self assembling systems for drug delivery…
Using this method she can control where a drug goes in the body, (particularly vital when a drug may be toxic and needs to be accurately targeted to a specific place like a tumour) and the speed at which the drug is released. The polymer self assembles in water to protect the hydrophobic ‘tail’ attached to it. The polymer is a bit like a comb, a molecular comb, with the polymer as the backbone and the hydrophobic tails as the teeth. The team have been working with polymers with low, medium and high levels of hydrophobic tails attached and depending on the ratio, the polymer will self-assemble into different architectures when added to water.
With a high number of hydrophobic chains, the polymer coalesces into a gel and can be used as a method of delivering drugs to the body. Other teams around the world have been able to load 4-5% of a gel with a treatment drug, using a cross linking agent to covalently bind the polymer chains. The reaction which creates the covalent linkages could destroy a drug added to the gel so most producers must make the gel first and then add the drug afterwards. Professor Uchegbu’s team have come up with a whole new way of creating the polymer gel which allows for a far higher percentage of the gel to be loaded with the drug.
“It's a bit like baking a cake” says Professor Uchegbu, “You start off with a wet mixture which you put in the oven and after it's baked the water has been largely removed by the baking process and the mixture is all stuck together. We do the same thing with our polymer gel. We put the drug into the mix with the polymer and the hydrophobic tails, then remove the water by freeze drying. The hydrophobic tails hold the polymer together so no covalent linkage is required. Because we add the drug before the gel is formed, we can load up to 40% of the gel with the drug. The gel will rehydrate in the moist environment of the body and gradually release the drug. Increasing the number of hydrophobic chains slows down the drug’s release into the body so it's possible to control the rate at which the drug is released quite accurately."
Add intermediate levels of hydrophobic chains and the polymer will create vesicles: small bubbles or sacs which form around the hydrophobic chain to protect it from the water. It is possible to place drug molecules within the vesicles and in this way deliver the drug to the patient. The size of the vesicle can be controlled by dictating the molecular weight of the polymer and this ability to control the size of the vesicle can be used to dictate which blood vessels the vesicle can pass through. Vesicles can be created which are too large to pass through the narrow blood vessels in healthy tissue but which are able to permeate the wider vasculature of a tumour. The vesicle is therefore a useful vehicle for drug delivery, transporting drugs more easily across the cell membrane and could be particularly useful in delivering drugs which are difficult to get into a cell with existing methods. The team also undertook research to look into the possibility of using vesicles to deliver genes directly into cells but so far this area has met with more limited success. Associating the drug encapsulated within the vesicle with DNA, however, allows the drug to be specifically targeted to an area within the body.
With a low number of hydrophobic chains the polymer doesn’t self assemble in water, despite the presence of hydrophobic groups and instead becomes soluble. This allows potential for delivering a drug to the body which is not normally soluble in water. Within the solution, invisible to the eye, tiny micelles are formed to shield the hydrophobic content. These micelles act as a hydrophobic pocket into which a drug can be put.
Working at the forefront of pharmaceutical research the team are also investigating small star shaped molecules called dendremas to efficiently deliver genes to specific areas in the body. At the moment chemicals used to deliver genes tend to allow gene expression in the blood vessels of the lungs, which limits the kinds of diseases which can be targeted. Professor Uchegbu’s team use molecules with very small molecular weight and they are able to deliver genes into the liver which is a much more useful area of the body in terms of the number of diseases which can be targeted and can allow gene expression to take place directly within tumours. With such a range of useful areas within her remit Professor Uchegbu is an asset to Scotland and the world of drug delivery systems. One day many of us may benefit from the fruits of her labours, although hopefully not too soon!