Tuesday, March 29, 2016

PLGA from PolySciTech investigated for in-situ delivery of doxorubicin for treatment of liver cancer

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers and polyesters. This includes PLGA (PolyVivo AP031) which has recently been used in a study relating to localized delivery of doxorubicin to a tumor site. There are many advantages to providing localized delivery, especially for chemotherapeutics, as this reduces systemic toxicity to whole body while maintaining a therapeutic concentration directly at the tumor site. One means of doing this is to dissolve a biodegradable polymer (such as PLGA) in a water-miscible, biocompatible organic solvent such as N-methyl-2-pyrrolidinone (NMP) along with the drug to be delivered. When this solution is introduced into the body, the NMP extracts out quickly with the surrounding bodily fluids leaving a solid PLGA form containing the drug. This is referred to as an ‘in-situ implant’ because the solid implant is actually formed inside the body itself. From this point forward, the drug leaches slowly out of the PLGA by diffusion and degradation, providing an extended delivery system which provides drug directly to the local tissues. A major advantage to using this system is direct, local application of the medicine. This is unlike systemic application. The majority of medicine which is administered systemically (for example, a traditional IV injection) never reaches the location of action. Instead, the body’s natural screening mechanisms, remove the drug from the blood by the kidneys and it ends up in the urine, or it is removed by other pathways.  Recently, researchers used in-situ formation technique to deliver PLGA encapsulated doxorubicin to model liver-cancer tumors. Liver cancer is normally resistant to traditional chemotherapy. They found that the tumors had significantly reduced progression after 21 days from this doxorubicin delivery method which holds promise as a treatment method. Read more: Solorio, Luis, Hanping Wu, Christopher Hernandez, Mihika Gangolli, and Agata A. Exner. "Ultrasound-guided intratumoral delivery of doxorubicin from in situ forming implants in a hepatocellular carcinoma model." Therapeutic Delivery 7, no. 4 (2016): 201-212. http://www.future-science.com/doi/abs/10.4155/tde-2015-0008

“Abstract: Background: Hepatocellular carcinomas are frequently nonresponsive to systemically delivered drugs. Local delivery provides an alternative to systemic administration, maximizing the dose delivered to the tumor, achieving sustained elevated concentrations of the drug, while minimizing systemic exposure. Results: Ultrasound-guided deposition of doxorubicin (Dox)-eluting in situ forming implants (ISFI) in an orthotopic tumor model significantly lowers systemic drug levels. As much as 60 µg Dox/g tumors were observed 21 days after ISFI injection. Tumors treated with Dox implants also showed a considerable reduction in progression at 21 days. Conclusion: Dox-eluting ISFIs provide a promising platform for the treatment of hepatocellular carcinomas by which drug can be delivered directly into the lesion, bypassing distribution and elimination by the circulatory system.”
Post a Comment