Monday, August 1, 2016

PEG-PLGA and PLGA from PolySciTech used for mechanistic study of nanoparticle binding to tumor tissue

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers and biodegradable block copolymers for research applications. Recently, researchers at the University of Maryland utilized mPEG-PLGA 5K-10K (PolyVivo Cat# AK010) and PLGA (PolyVivo AP081) to generate nanoparticles and then tracked these nanoparticles in regards to their uptake into tumor cells as compared to their non-specific binding towards extracellular matrix and other biological components. They found that PEG plays an important role in preventing non-specific binding. This research holds promise for improved therapeutic delivery strategies. Read more: Dancy, Jimena G., Aniket S. Wadajkar, Craig S. Schneider, Joseph RH Mauban, Olga G. Goloubeva, Graeme F. Woodworth, Jeffrey A. Winkles, and Anthony J. Kim. "Non-specific binding and steric hindrance thresholds for penetration of particulate drug carriers within tumor tissue." Journal of Controlled Release (2016). http://www.sciencedirect.com/science/article/pii/S0168365916304692

“Abstract: Therapeutic nanoparticles (NPs) approved for clinical use in solid tumor therapy provide only modest improvements in patient survival, in part due to physiological barriers that limit delivery of the particles throughout the entire tumor. Here, we explore the thresholds for NP size and surface poly(ethylene glycol) (PEG) density for penetration within tumor tissue extracellular matrix (ECM). We found that NPs as large as 62 nm, but less than  110 nm in diameter, diffused rapidly within a tumor ECM preparation (Matrigel) and breast tumor xenograft slices ex vivo. Studies of PEG-density revealed that increasing PEG density enhanced NP diffusion and that PEG density below a critical value led to adhesion of NP to ECM. Non-specific binding of NPs to tumor ECM components was assessed by surface plasmon resonance (SPR), which revealed excellent correlation with the particle diffusion results. Intravital microscopy of NP spread in breast tumor tissue confirmed a significant difference in tumor tissue penetration between the 62 and 110 nm PEG-coated NPs, as well as between PEG-coated and uncoated NPs. SPR assays also revealed that Abraxane, an FDA-approved non-PEGylated NP formulation used for cancer therapy, binds to tumor ECM. Our results establish limitations on the size and surface PEG density parameters required to achieve uniform and broad dispersion within tumor tissue and highlight the utility of SPR as a high throughput method to screen NPs for tumor penetration. Graphical abstract: Nanoparticle (NP) penetration was visualized via intravital microscopy after direct injection into flank tumors. Uncoated NPs were immobilized at the tumor injection site and densely PEG-coated NPs as large as 63 nm penetrated into the tumor. Keywords: Nanoparticles; PEG density; Tumor tissue penetration; Surface plasmon resonance (SPR); Multiple particle tracking (MPT); Intravital microscopy”
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