John Garner

mPEG-PLGA from PolySciTech used in investigation on nanoparticle interactions with the lymphatic system

Blog Post created by John Garner on Feb 4, 2019

Howard, 2019 PEG-PLGA lymphatic tracking.jpg

One method to provide for improved vaccines with high potency is to target the delivery system to enable maximum exposure to immune cells. A strategy to accomplish this is to generate nanoparticles which are designed to be uptaken by the lymph nodes for good exposure to lymphocyte cells. The interactions between nanoparticles and cells are driven by many factors including biochemical (charge, specific interactions) and physical (size) parameters. Recently, researchers working at Johns Hopkins University, Yale University, and University of Florida used PEG-PLGA (AK101) from PolySciTech (www.polyscitech.com) to investigate nanoparticle movement in respect to the lymphatic system relative to nanoparticle size. This research holds promise to provide further understanding of how particles interact with living bodies to enable development of advanced drug-delivery particles for vaccines. Read more: Howard, Gregory P., Garima Verma, Xiyu Ke, Winter M. Thayer, Timothy Hamerly, Victoria K. Baxter, John E. Lee, Rhoel R. Dinglasan, and Hai-Quan Mao. "Critical size limit of biodegradable nanoparticles for enhanced lymph node trafficking and paracortex penetration." Nano Research: 1-8. https://link.springer.com/article/10.1007/s12274-019-2301-3

“Abstract: Lymph node (LN) targeting through interstitial drainage of nanoparticles (NPs) is an attractive strategy to stimulate a potent immune response, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective “size gate” for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol) (PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retained in LNs more effectively than NPs with a number average diameter of 40-nm. The drainage of 100-nm NPs was negligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines. Keywords: biodegradable nanoparticle lymph node trafficking vaccine delivery nanoparticle size antigen presenting cells in vivo imaging”

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