Wednesday, March 15, 2017

PolySciTech mPEG-PLGA and PLGA-Rhodamine products used in development of advanced chemoradiotherapy delivery system

Chemoradiotherapy is a cancer therapy technique in which a sensitizer molecule is administered to a patient prior to administration of a dose of radiation. Typically, such a technique is made difficult as the sensitizer molecule can affect both tumor tissue and normal tissue, causing more damage from radiation. However, with the application of localized-delivery to the tumor, this technique holds great potential for cancer therapy by allowing specific and selective destruction of tumor tissue at a relatively lower dose of radiation.  Recently, researchers at the University of North Carolina Chapel Hill utilized PolySciTech (www.polyscitech.com) mPEG-PLGA’s (PolyVivo AK010, AK023) and fluorescently-tagged polymer PLGA-rhodamine B (PolyVivo AV011) for development of an advanced nanoparticle delivery system for Wortmannin (DNA-PK inhibitor) or novel KU60019 (ATM inhibitor) molecules. Both of these molecules act to increase local radiation damage to tumors by preventing DNA repair. The researchers found that smaller particles were more effective at avoiding hepatic clearance but medium sized particles showed more efficacy for sensitization. This research holds promise for enhanced cancer treatment techniques. Read more: Caster, Joseph M., K. Yu Stephanie, Artish N. Patel, Nicole J. Newman, Zachary J. Lee, Samuel B. Warner, Kyle T. Wagner et al. "Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy." Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300448

“Abstract: Nanoparticle (NP) therapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend towards enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application. Graphical Abstract: Sub50 nm drug-loaded NPs avoid hepatic clearance and more homogeneously distribute within tumors. However, they are no more efficacious and are associated with more small bowel toxicity than larger particles. Keywords: Nanoparticle; Chemoradiotherapy; Nanoparticle radiosensitization; KU60019; Wortmannin”


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