Biodegradable Polymers for Drug and Gene Delivery

Reading time: 4 – 6 minutes

In participation with Blog Action Day, an event where bloggers from around the world unite to put a single important issue on everyone’s mind – the environment – today’s article discusses recent advances in the use of biodegradable materials for drug and gene delivery.

Drug delivery

Last month, we discussed how green chemistry was recently used by two research groups to mimic the cellular process of drug synthesis, imitating complex biosynthetic processes outside the cell to create antibiotics. Green chemistry attempts to reduce or eliminate the generation and use of hazardous substances in the design and development of chemical products and processes, minimizing its impact on patients and the environment.

Now chemists at the University of Nottingham are using green chemistry to develop new methods for coating drugs in plastics [1]. While conventional methods use high temperatures and volitile solvents such as benzene and chloroform, green chemistry techniques allow for the coating of drugs without damaging or degrading the active ingredients. This means the drugs are free of toxic chemical residues and are more effective.

The Clean Technology Group at Nottingham is exploiting the use of supercritical carbon dioxide, which under high pressure at room temperature is a solvent that can use biodegradable plastics to make polymer drug coatings [2]. The polymer (meaning a material composed of molecules with repeating structural units that form a long chain) is used to encapsulate a drug prior to injection in the body and is based on lactic acid, a compound normally produced in the body, and is thus able to be excreted naturally. The coating is designed for controlled release over a period of time, reducing the number of injections required and maximizing the therapeutic benefit.

Professor Steve Howdle, whose research is focused on exploiting the unique properties of supercritical carbon dioxide, said [1]:

Biodegradable polymers are particularly attractive for use in drug delivery, as once introduced into the body they require no retrieval or further manipulation and are degraded into soluble, non-toxic by-products. Different polymers degrade at different rates within the body and therefore polymer selection can be tailored to achieve desired release rates.

Gene delivery

Another interesting recent development is a report by MIT researchers that they have found a way to create gene carriers from biodegradable polymers instead of viral materials [3].

Gene therapy is the introduction of a gene or genes into the cells of a tissue to treat disease. Although 1,180 gene therapy clinical trials have been conducted since 1989 [4], there are no FDA-approved gene therapies, in part because viruses are used as gene carriers. Viruses present a number of potential problems, including toxicity, immune response and targeting issues.

The MIT study focused on three poly(beta-amino-esters) chains of alternating amine and diacrylate groups that spontaneously assemble with DNA to form nanoparticles when mixed together. The polymer-DNA nanoparticle can act like an artificial virus and deliver DNA when injected into tissue. Researchers chemically modified the ends of the polymer chains using a library of small molecules to attenuate and optimize nanoparticle formation and DNA delivery.

According to Daniel Anderson, the study leader and research associate in MIT’s Center for Cancer Research [5]:

Just by changing a couple of atoms at the end of a long polymer, one can dramatically change its performance. These minor alterations in polymer composition significantly increase the polymers’ ability to deliver DNA, and these new materials are now the best non-viral DNA delivery systems we’ve tested.

Degradable polymers are used in dissolvable stitches and have been utilized in the pharmaceutical industry in various forms for decades. Using the technologies described above, not only are we able to produce purer products that offer therapeutic benefits, but both the processes and products are cleaner and safer for the environment.

References

1. Using green chemistry to deliver cutting-edge drugs. The University of Nottingham. 2007 Sep 13.
2. Tai et al. Putting the fizz into chemistry: applications of supercritical carbon dioxide in tissue engineering, drug delivery and synthesis of novel block copolymers. Biochem Soc Trans. 2007 Jun;35(Pt 3):516-21.
   View abstract
3. Green et al. Combinatorial Modification of Degradable Polymers Enables Transfection of Human Cells Comparable to Adenovirus. Advanced Materials. 2007 Oct;19(19):2836-42.
4. Gene Therapy Clinical Trials Worldwide. Provided by the Journal of Gene Medicine. Updated 2007 July.
5. MIT works toward safer gene therapy. MIT News. 2007 Sep 7.