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• W2339781208 abstract "Event Abstract Back to Event Efficient tumor penetration of a rationally engineered nanoparticle Yang Yang1*, Aniruddha Roy1* and Shyh-Dar Li1* 1 The University of British Columbia, Faculty of Pharmaceutical Sciences, Canada Introdution: Poor penetration in solid tumors has been one of the major challenges limiting the antitumor efficacy of nanomedicines. Intratumoral transport barriers include the abnormal blood flow, heterogeneous architecture of the vascular network, dense nature of the extracellular matrix and interstitial hypertension[1],[2]. We have developed a polysaccharide conjugate nanoparticle system for drug delivery to solid tumors. Podophyllotixin (PPT, an anti-tubulin drug) and polyethylene glycol (PEG) were covalently conjugated to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages. Nanoparticles with different properties could be fabricated from the conjugates by self-assembly in saline. We examined how PPT-to-PEG ratio in the conjugate affected the size, drug release and cell killing potency of the resulting nanoparticles. We also compared the tumor delivery and penetration of these different nanoparticles in a tumor spheroid system and an s.c. tumor in mice. Materials and Methods: Conjugates with various PPT/PEG ratios (2-20 molar ratios) were synthesized, and nanoparticles were prepared from these conjugates[3]. Nanoparticles were compared for particle size, drug release, potency, tumor delivery and penetration in a tumor spheroid system and an s.c. tumor in mice. Results and Discussion: The size of the resulting nanoparticles increased with the increased PPT/PEG ratio. For example, the conjugate of a PPT/PEG ratio of 20 yielded 120 nm particles, while 20 nm particles were produced with the conjugate of a PPT/PEG ratio of 2. Drug release rate increased along with decreased size and PPT/PEG ratio. The drug release rates for the 20, 30 and 120 nm particles were 5%, 2.5% and 1%/day, respectively. The 20 nm particles exhibited 2- to 5-fold enhanced cell killing activity and 5- to 20-fold increased delivery to an s.c. tumor compared to the 30 nm and 120 nm particles. In tumor spheroids, the penetration of three nanoparticles constructed was significantly different: the tumor penetration efficiency of the nanoparticles followed the order of 20 nm > 30 nm > 120 nm. The 20 nm particles penetrated the EMT6 tumor spheroids thoroughly in 3 h, while the 120 nm particles displayed little penetration. The in vivo data were consistent with the spheroid data: within the s.c. tumor, >90% of the 20 nm particles penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. Conclusion: By varying the PPT/PEG ratio in the conjugates, nanoparticles with different physicochemical properties (size, drug release kinetics, potency) could be prepared. The 20 nm particles displayed significantly improved delivery to tumor and enhanced tumor penetration compared to the larger counterparts. References:[1] Minchinton, A.I., Tannock, I.F. Drug penetration in solid tumours. Nat. Rev. Cancer 2006; 6: 583–592.[2] Chauhan V.P., Stylianopoulos T., Boucher Y., Jain R.K. Delivery of molecular and nanoscale medicine to tumors: transport barriers and strategies. Annu. Rev. Chem. Biomol. Eng. 2011; 2: 281–298.[3] Aniruddha Roy, Mark J. Ernsting, Elijus Undzys, Shyh-Dar Li. A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors, Biomaterials 2015; 52: 335-346. Keywords: Drug delivery, biomaterial, polymer Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for therapeutic delivery Citation: Yang Y, Roy A and Li S (2016). Efficient tumor penetration of a rationally engineered nanoparticle. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01222 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Yang Yang, The University of British Columbia, Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada, Email1 Dr. Aniruddha Roy, The University of British Columbia, Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada, aniroy@mail.ubc.ca Dr. Shyh-Dar Li, The University of British Columbia, Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada, shyh-dar.li@ubc.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yang Yang Aniruddha Roy Shyh-Dar Li Google Yang Yang Aniruddha Roy Shyh-Dar Li Google Scholar Yang Yang Aniruddha Roy Shyh-Dar Li PubMed Yang Yang Aniruddha Roy Shyh-Dar Li Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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• W2339781208 title "Efficient tumor penetration of a rationally engineered nanoparticle" @default.
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