Controlled Drug Release from Biomaterial Surfaces

Controlled Drug Release with Biomaterials

Join and beta test materials that you can modify easily for controlled drug release.

Introduction to Controlled Drug Release using Biomaterials

There are several applications of easy-to-modify biomaterial surfaces ranging from capture of circulating tumor cells to efficient suspension culture of pluripotent stem cells …today, let’s talk about how we can use them for controlled drug release.

The main reason for releasing drugs from surfaces is to treat diseases locally. As an example, think of a stent — a metal structure that’s placed inside blood vessels when patients have blocked blood vessels. Typically, stents are bare metals formed into an expandable device that can be released from a catheter and prop open a blood vessel. See this picture to get an idea of what this looks like:
Stenosis and Controlled Release

When the stent expands, it opens up the blood vessel. But, cells will soon grow into the walls of the stent and occlude the blood vessel once again (this is called restenosis). However, if we had a stent that released a drug like paclitaxel or methotrexate to prevent cells from growing into the stent, there’s proof that restenosis can be prevented for prolonged periods of time –this is controlled release. The drug will be much more effective if its release happens over the course of a few weeks. Hence, we can release drugs locally where the drug is necessary and avoid systemic injection and circulation. Systemic methotrexate can lead to myelosuppression (bone marrow makes less red blood cells) or mucositis (painful inflammation of mucus tracts). Take a look at the picture here:

Biomaterial Methotrexate Release

Current Challenges of Controlled Drug Release

Controlled release using biomaterial surfaces is incredibly valuable, but also challenging. As you may know, biomaterials that are hydrophobic tend to illicit stronger immune reactions than those that are hydrophilic. However, a large majority of drugs are hydrophobic. Thus, encapsulating hydrophobic drugs with hydrophilic surfaces is a challenge (A, below). Take a look at the pictures below.

Hydrogels, which are chemically cross-linked hydrophilic polymers, are a great tool for controlled drug release. They are hydrophilic and incredibly biocompatible due to their large water content. When placed in water, hydrogels expand rapidly and have excellent surface area where drug can be attached and released. However, as you might expect, drugs attached to the hydrogels tend to release in a burst because they are exposed to water/solution as soon as they are implanted (B, below). Initially a lot of drug is released and over time the rate of drug release tapers off. Furthermore, hydrogels tend to have low tensile strength because of how much they swell in water.

With regard to stents, two additional challenges are: drug eluting materials need to withstand sterilization, and long-term, stents should endothelialize while retarding smooth muscle cell growth(C, below). The first of these challenges is true for any biomaterial surface that is used in vivo. Without the ability to easily undergo ethylene oxide sterilization (as is the case with stents) or be autoclaved (as it is with liquid materials), no material can be implanted inside the body. Regarding the second challenge, endothelialization is important because long-term, we want the patient’s blood vessel wall to become normal. Blood vessels are normally lined with endothelial cells (which contact blood) and below them there are smooth muscle cells (which give structure but don’t contact blood). Surfaces without endothelial growth will thrombose (get blood clots) and lead to dangerous long-term pathologies. Smooth muscles, the primary reason for restenosis, however, need to be retarded and prevented from growing uncontrollably.

Challenges of Controlled Release with Biomaterials

Using Functional Biomaterials for Controlled Drug Release

Biomaterials that are easy to functionalize represent a great platform to solve challenges in controlled release. Consider a hydrophobic polymer surface which has amine functional groups. Immobilizing hydrophobic drugs on this functional hydrophobic surface would be much simpler than inside a hydrophilic hydrogel.

Burst release from a surface could be controlled with the linker. Using enzymatically cleavable linkers or different types of chemical linkers like esters, may help provide the correct drug release timeline. Perhaps such linkers could be incorporated on a polymer surface like these functionalizable biosurfaces and drug release could be tailored.

For better stent design, what if we could have a biomaterial to release methotrexate from some areas while also promoting vascularization on other areas of the surface. This could be achieved by patterning a easy-to-modify polymer coating with methotrexate & immobilizing anti-CD34 antibodies so we can recruit endothelial cell precursors to the stent.

See the images below for an idea of how functional biomateials can aid controlled drug release.

How Biomaterials solve challenges in controlled release

References

Review on improving Endothelialization of Stents

Challenges of Hydrogel drug delivery

Application of controlled release in stents

Improving methotrexate-eluting stents

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