Polymer-drug Conjugates

Mia Madduri

In America cancer is second among the leading causes of death in adults. Traditional treatments to cancer, which accounts for about one in four deaths, include chemotherapy, radiation therapy, and surgery (American Cancer Society, 2014). However, with these treatments, not only is the tumor affected, but the rest of the patient’s body is also affected. Chemotherapy and radiation therapy stop the production of rapidly splitting cells in the body in order to prevent the cancerous cells from spreading. Chemotherapy works by damaging the genes of cells that are rapidly dividing. Chemotherapy drugs can be administered orally or through an intravenous drip (Cancer Research UK, 2013). Radiation therapy works and is administered essentially the same way. This result means that healthy tissue can be damaged; using this treatment patients lose their hair and appetite after a bout of chemotherapy. The rapidly growing cells in healthy tissues die, such as cells in follicles, bone marrow, and lining of the digestive system (American Cancer Society, 2014). The side effects of traditional forms of treatment often also cost more money, adding to the stress of the patient and family. With the use of an alternative treatment, called polymer-drug conjugates, a more efficient treatment is now a possibility.

There are many benefits to combining nanosized polymers and drugs. This concept, however, has been around for a while. In the 1970s, Ringsdorf proposed the first model of a combination of chemotherapeutic drugs (drugs mainly used to treat cancer) and biocompatible polymers. Since then, many advances have been made to send these conjugates to trial, and have revolutionized treatment for diseases such as cancer, diabetes, and others (Li, 2008; Sanchis, 2010). The idea proposed by Ringsdorf combined polymers and drugs covalently (Pang, 2013). The process involves a bioagent covalently bonding to a polymeric backbone to form a polymer-drug conjugate. If a bioagent is previously insoluble in water and is combined with a polymer that is water-soluble, the resulting conjugate can be water-soluble also. This makes many previously unusable drugs available for treatment because of their increase in aqueous solubility. Drugs insoluble in water cannot be taken by humans because our body environment is aqueous and would reject the drug. The chemistry behind it is basic: polar molecules dissolve other polar molecules. Hydrophobic (literally “water fearing”) drugs are not polar molecules and therefore, are not typically viable as a treatment; however, when combined with certain hydrophilic “water liking” polymers, this process changes the polarity of the drug and can become hydrophilic also, increasing the solubility of the drug in an aqueous solution (Pang, 2013).

More importantly, these conjugates can be administered to a site through targeted drug delivery, which essentially makes more molecules of the drug available at the specific location (Li, 2008). This method of drug delivery has been shown to be extremely effective, particularly when administering chemotherapeutic drugs. The benefits of this (referent) is a more direct form of treatment; by using nanosized polymers to deliver the drugs, the drug is delivered more specifically to the site of infection. These drugs can either passively or actively target the delivery site, whether it is a tumor or infection. Through passive targeting, the nanosized polmyer-drug is administered and can find the site due to the inflamed nature of the tissue. Active targeting employs the use of ligands that specifically bind to the site (Li, 2008). Traditional chemotherapy treatments end up slowing the growth of even healthy tissues, causing the common side effect hair loss along with loss of appetite and nausea (American Cancer Society, 2014). Using targeted drug delivery is expected to help keep healthy tissues from being damaged, and save money in terms of reducing side effects.

The benefits of using biocompatible polymers extend to while the drug is at the drug delivery site. Once the drug-loaded nanoparticle reaches the delivery site, it doesn’t immediately dissolve. New drugs, called prodrugs, have been used to help preserve the drug until it needs to be activated. Prodrug reconversion is the process of converting the inactive form of the drug to the active form. To initiate this conversion, pH and certain enzymes can release the drugs. In certain pH the drug starts to degrade, allowing the body to absorb the drug. Certain amylases and enzymes can degrade the drug also. Having an inactive form of the drug is beneficial because the drug can be administered, and until a change in homeostasis occurs, the drug will be preserved at the delivery site (Vincent, 2006). By combining prodrugs with polymers, the advantages also include increased water-solubility of otherwise insoluble drugs and specific targeting of the drug delivery site discussed previously, preservation of drug until activation, and eliciting less of an immunological body response (Vincent, 2006).

Although the benefits are great, there are also challenges to the development of polymer-drug conjugates For example, the conjugates can be volatile and unstable in a human body. For example, clinical trials show a prodrug initially being preserved at the drug delivery site, but suddenly degrade and release the drug at the wrong time. Also, the use of enzymes to degrade the drug can change how much the surrounding cells absorb and how much of the drug is distributed across the body (Khandare, 2006). However, once these problems are dealt with, these conjugates offer more precise treatment for a variety of diseases other than cancer. Diabetes, rheumatoid arthritis, infection, hypertensions, or intestinal diseases are some examples of where polymer-drug conjugates would be useful. These conjugates can be used to help with tissue restoration, wound healing, and bone resorption (bone resorption is the process where osteoclasts break down bone to release minerals, and ischemia, loss of blood to organs) (Sanchis, 2010).

Works Cited

Pang, Xin, Hong-Liang Du, Hai-Qun Zhang, Ying-Jie Zhai, and Guang-Xi Zhai. “Polymer–drug Conjugates: Present State of Play and Future Perspectives.” Drug Discovery Today 18.23-24 (2013): 1316-322. ScienceDirect. Web. 15 Jan. 2014. <http://www.sciencedirect.com/science/article/pii/S1359644613003115>.

Vincent, María J., and Ruth Duncan. “Polymer Conjugates: Nanosized Medicines for Treating Cancer.” Trends in Biotechnology 24.1 (2006): 39-47. ScienceDirect. Web. 15 Jan. 2014. <http://www.sciencedirect.com/science/article/pii/S0167779905003021>.

Li, Chun, and Sydney Wallace. “Polymer-drug Conjugates: Recent Development in Clinical Oncology.” Advanced Drug Delivery Reviews 60.8 (2008): 886-98. ScienceDirect. Web. 15 Jan. 2014. <http://www.sciencedirect.com/science/article/pii/S0169409X08000434>.

Sanchis, Joaquin, Fabiana Canal, Rut Lucas, and María J. Vicent. “Polymer–drug Conjugates for Novel Molecular Targets.” Nanomedicine 5.4 (2010): 915-35. ScienceDirect. Web. 15 Jan. 2014. <http://www.futuremedicine.com/doi/pdf/10.2217/nnm.10.71>.

Khandare, Jayant, and Tamara Minko. “Polymer–drug Conjugates: Progress in Polymeric Prodrugs.” Progress in Polymer Science 31.4 (2006): 359-97. ScienceDirect. Web. 15 Jan. 2014.

“How Chemotherapy Works.” : Cancer Research UK : CancerHelp UK. 7 Mar. 2013. Web. 10 Feb. 2014. <http://www.cancerresearchuk.org/cancer-help/about-cancer/treatment/chemotherapy/about/how-chemotherapy-works>.

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