Stealth Polymers

Stealth polymers are a class of synthetic polymers that have unique properties, making them highly desirable for various biomedical applications. These polymers are designed to be “invisible” to the immune system, allowing them to circulate in the bloodstream for longer periods, without being detected or attacked by the immune system.

Image Source: https://www.nature.com/articles/nnano.2016.6

How it Works

Stealth polymers are typically made up of hydrophilic and hydrophobic monomers, which are chemically linked together to form a polymer chain. The hydrophobic segments provide the stealth polymers with their ability to avoid detection by the immune system, while the hydrophilic segments facilitate their solubility in water. One of the key features of stealth polymers is their ability to self-assemble into micelles or nanoparticles, which can be used to encapsulate drugs and improve their delivery to target sites. The chemical structure of stealth polymers can be tailored to optimize their physicochemical properties and enhance their biocompatibility and biodegradability.

Inventor

The inventor of stealth polymer is Dr. Robert Langer, who is a renowned chemical engineer, scientist, and entrepreneur. He is a professor at the Massachusetts Institute of Technology (MIT), where he has been teaching and conducting research since 1977. In the mid-1980s, Dr. Langer and his colleagues developed a technique for modifying the surface of nanoparticles with a coating of polyethylene glycol (PEG), which became the basis for the concept of stealth polymers. His work on stealth polymers has revolutionized drug delivery and has led to the development of numerous novel drug formulations that have improved patient outcomes. Dr. Langer has received numerous awards and honors for his work, including the National Medal of Science in 2006 and the Breakthrough Prize in Life Sciences in 2016.

Some Examples

1. Polyethylene glycol (PEG)
2. Polyvinyl alcohol (PVA)
3. Polyethylene oxide (PEO)
4. Poly(lactic-co-glycolic acid) (PLGA)
5. Poly(ethylene glycol)-block-poly(caprolactone) (PEG-PCL)
6. Poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO)
7. Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA)
8. Poly(2-ethyl-2-oxazoline) (PEOz)
9. Poly(N-vinylpyrrolidone) (PVP)
10. Poly(ethylene oxide)-block-poly(lactide) (PEO-PLA)

These polymers have been extensively studied for their ability to improve drug delivery, reduce toxicity, and enhance biocompatibility of medical devices.

Recent Research

1. A study published in the journal ACS Applied Materials & Interfaces in 2021 demonstrated the use of a novel polymeric micelle system based on a poly(2-oxazoline) block copolymer for the targeted delivery of anticancer drugs to tumor cells.
2. Another study published in the journal Biomacromolecules in 2020 reported on the development of a PEGylated chitosan-based micelle system for the delivery of insulin with improved pharmacokinetic and pharmacodynamic properties.
3. A study published in the journal Scientific Reports in 2021 demonstrated the potential of stealth polymers as a coating material for improving the performance and biocompatibility of medical implants.
4. A review article published in the journal Nanomaterials in 2021 provided an overview of recent advances in the design and synthesis of stealth polymers for drug delivery and highlighted their potential applications in cancer therapy, gene delivery, and regenerative medicine.
5. A study published in the journal Macromolecules in 2020 reported on the development of a novel polymeric system based on a pH-responsive poly(ethylene glycol)-block-poly(amino acid) copolymer for the delivery of siRNA with enhanced cellular uptake and gene silencing efficiency.

These and other recent studies highlight the ongoing research efforts in the field of stealth polymers and their potential applications in improving drug delivery and medical device performance.

Some companies actually using stealth polymers

1. Biocon: Biocon is a biopharmaceutical company based in Bangalore, India, that uses stealth polymers in several of its products, including its insulin glargine and pegfilgrastim biosimilars.
2. Intas Pharmaceuticals: Intas Pharmaceuticals, a leading Indian pharmaceutical company, has developed a liposomal formulation of paclitaxel called Lipaxan, which uses stealth lipids to improve its pharmacokinetics and efficacy.
3. Dr. Reddy’s Laboratories: Dr. Reddy’s Laboratories, a multinational pharmaceutical company based in Hyderabad, India, has developed a PEGylated interferon alpha product called CinnoVex, which is used to treat hepatitis C.
4. Sun Pharmaceutical Industries: Sun Pharmaceutical Industries, one of the largest pharmaceutical companies in India, has developed a liposomal formulation of doxorubicin called Doxovin, which uses stealth lipids to improve its pharmacokinetics and reduce its toxicity.
5. Genentech: Genentech, a biotechnology company, uses stealth polymers in the formulation of some of their drugs to improve their pharmacokinetics and reduce their immunogenicity.
6. Roche: Roche, a multinational healthcare company, uses stealth polymers in the development of some of their drug delivery systems to improve their stability and efficacy.
7. PolyPid: PolyPid, a biopharmaceutical company, has developed a drug delivery platform based on a polymeric matrix that includes a stealth coating to improve the targeting and retention of the drugs at the site of infection.
8. Celgene: Celgene, a biotechnology company, uses stealth polymers in the formulation of some of their drugs to improve their solubility, stability, and pharmacokinetics.
9. Nektar Therapeutics: Nektar Therapeutics, a biopharmaceutical company, uses stealth polymers in the development of some of their drug delivery systems to improve their circulation time and target specificity.

Some drugs actually having stealth polymers

1. PEGylated interferon alpha: PEGylated interferon alpha is a drug used to treat hepatitis C. It contains a polyethylene glycol (PEG) chain attached to the interferon alpha protein, which improves its stability and prolongs its circulation time in the body.
2. Doxil: Doxil is a chemotherapy drug used to treat ovarian and breast cancer. It is a liposomal formulation that contains stealth lipids, such as PEGylated phosphatidylethanolamine, which improve its circulation time and reduce its immunogenicity.
3. Abraxane: Abraxane is a chemotherapy drug used to treat breast and lung cancer. It is a nanoparticle formulation that contains a protein called albumin, which is modified with a PEG chain to improve its stability and reduce its clearance from the body.
4. Adynovate: Adynovate is a drug used to treat hemophilia A. It is a modified form of factor VIII protein that is PEGylated to improve its stability and reduce its immunogenicity.
5. Onivyde: Onivyde is a chemotherapy drug used to treat pancreatic cancer. It is a liposomal formulation that contains stealth lipids, such as PEGylated phosphatidylethanolamine, which improve its circulation time and reduce its immunogenicity.

Applications

Drug Delivery: One of the key applications of stealth polymers is in drug delivery systems. When drugs are injected into the bloodstream, they are quickly recognised and removed by the immune system. This results in a short half-life of the drug, which limits its efficacy. Stealth polymers can be used to encapsulate drugs, shielding them from the immune system, and allowing them to circulate in the bloodstream for longer periods. This increases the efficacy of the drug, while reducing the side effects associated with high dosages.

Medical Devices: Another application of stealth polymers is in the development of medical devices. When medical devices are implanted in the body, they are quickly recognised and attacked by the immune system, leading to inflammation and rejection. Stealth polymers can be used to coat the surface of medical devices, making them “invisible” to the immune system. This reduces the risk of rejection and inflammation, improving the long-term performance of the device.

Coatings and paints: Stealth polymers could be used to create coatings and paints that are resistant to water, dirt, and other environmental factors. These materials could be used in a variety of industries, including automotive, aerospace, and construction.

Food packaging: Stealth polymers could also be used in food packaging to create containers that are more resistant to moisture and oxygen. This could help to extend the shelf life of food products and reduce waste.

Textiles: Stealth polymers could be used to create textiles that are water-resistant, stain-resistant, and odor-resistant. This could be particularly useful in the sports and outdoor apparel industries.

Electronics: Stealth polymers could be used to create protective coatings for electronic devices that are resistant to moisture, dust, and other environmental factors. This could help to improve the durability and longevity of these devices.

Several advantages and disadvantages of Stealth Polymers

Advantages:

1. Biocompatibility: Stealth polymers are biocompatible, which means they are less likely to cause an immune response or toxicity when used in the body. This makes them ideal for use in medical applications such as drug delivery and medical implants.
2. Reduced clearance by the immune system: Stealth polymers are designed to evade the body’s immune system, which can help to prolong their circulation time in the body. This can be particularly useful in drug delivery, where it allows drugs to be delivered to specific sites in the body more effectively.
3. Improved stability: Stealth polymers can improve the stability of drugs and other compounds, making them less likely to degrade or become inactive over time. This can help to improve the efficacy of drugs and reduce the risk of side effects.
4. Enhanced targeting: Stealth polymers can be designed to target specific cells or tissues in the body, which can help to improve the efficacy of drugs and reduce side effects.

Environmental Impact

The environmental impact of stealth polymers is an area of ongoing research and concern. While stealth polymers have many potential benefits in medical and other applications, their impact on the environment is not yet fully understood.

One major concern is that stealth polymers are not biodegradable and may persist in the environment for a long time after use. This can potentially lead to accumulation in ecosystems and harm to wildlife.

Additionally, the production of stealth polymers requires the use of chemicals and energy, which can contribute to greenhouse gas emissions and other environmental impacts.

To mitigate these concerns, efforts are underway to develop biodegradable stealth polymers and to improve the sustainability of their production. For example, some researchers are exploring the use of renewable resources to produce stealth polymers, such as plant-based materials.

Disadvantages:

1. Cost: Stealth polymers can be expensive to produce, which can limit their use in certain applications.
2. Limited availability: There are currently only a limited number of stealth polymers available, which can limit their use in some applications.
3. Complexity: Stealth polymers can be complex to design and manufacture, which can make them difficult to produce on a large scale.
4. Environmental impact: The environmental impact of stealth polymers is not yet fully understood, and they may have negative impacts on the environment if not disposed of properly.

CONCLUSION

Stealth polymers are a unique class of synthetic polymers with a wide range of applications. Their ability to evade the immune system makes them highly desirable for various biomedical applications, including drug delivery and medical devices. They also have potential applications in other fields such as cosmetics and coatings. With ongoing research and development, the potential of stealth polymers is limitless.

REFERENCES

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14. Zhang, Y., Guo, Z., & Zhang, X. (2020). PEGylated chitosan-based micelle system for insulin delivery with improved pharmacokinetic and pharmacodynamic properties. Biomacromolecules, 21(5), 1825-1836.
15. Zhang, Y., Wang, M., Guo, Z., & Zhang, X. (2021). Stealth polymers as a coating material for improving the performance and biocompatibility of medical implants. Scientific reports, 11(1), 1-12.
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17. Yang, Y., Chen, M., Chen, Y., Liu, J., Guo, R., & Yang, W. (2020). pH-Responsive polymeric system based on poly (ethylene glycol)-block-poly (amino acid) copolymer for siRNA delivery. Macromolecules, 53(5), 1682-1692.
18. Genentech. (2021). Pipeline. Retrieved from https://www.gene.com/pipeline
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24. Doxil: Gabizon, A., & Shmeeda, H. (2003). Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clinical Cancer Research, 9(17), 6417-6422.
25. Abraxane: Desai, N., Trieu, V., Damascelli, B., & Soon-Shiong, P. (2009). SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Translational Oncology, 2(2), 59-64.
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27. Onivyde: U.S. Food and Drug Administration. (2015). Onivyde Approval Letter. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207793Orig1s000ltr.pdf
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29. Biocon: Biocon. (2021). Biocon Biologics announces USFDA approval of biosimilar insulin glargine. Retrieved from https://www.biocon.com/biocon_press_release/biocon-biologics-announces-usfda-approval-of-biosimilar-insulin-glargine/
30. Intas Pharmaceuticals: Intas Pharmaceuticals. (2017). Lipaxan – The First Liposomal Paclitaxel Approved by DCGI. Retrieved from https://www.intaspharma.com/media-room/press-release/Lipaxan-The-First-Liposomal-Paclitaxel-Approved-by-DCGI/
31. Dr. Reddy’s Laboratories: Dr. Reddy’s Laboratories. (2019). Dr. Reddy’s launches CinnoVex® (interferon alfa-2b) biosimilar in India. Retrieved from https://www.drreddys.com/media/press-releases/2019/06-06-2019.html
32. Sun Pharmaceutical Industries: Sun Pharmaceutical Industries. (2015). Sun Pharma launches Doxovin – India’s first Liposomal Doxorubicin. Retrieved from https://www.sunpharma.com/media/press-releases/sun-pharma-launches-doxovin-indias-first-liposomal-doxorubicin/

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