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Tailoring the supramolecular structure of amphiphilic glycopolypeptide analogue toward liver targeted drug delivery systems
Mohamed Wali, Aisha Roshan Zhou, Jie Ma, Shengnan He, Yiyan Yue, Dong Tang, James Z Gu, Zhongwei
Mohamed Wali, Aisha Roshan
Zhou, Jie
Ma, Shengnan
He, Yiyan
Yue, Dong
Tang, James Z
Gu, Zhongwei
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2017-04-07
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2017 IJP paper.pdf
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Abstract
Amphiphilic glycopolypeptide analogues have harboured great importance in the development of targeted drug delivery systems. In this study, lactosylated pullulan-graft-arginine dendrons (LP-g-G3P) was synthesized using Huisgen azide-alkyne 1,3-dipolar cycloaddition between lactosylated pullulan and generation 3 arginine dendrons bearing Pbf and Boc groups on the periphery. Hydrophilic lactosylated pullulan was selected for amphiphilic modification, aiming at specific lectin recognition. Macromolecular structure of LP-g-G3P combined alkyl, aromatic, and peptide dendritic hydrophobic moieties and was able to self-assemble spontaneously into core-shell nanoarchitectures with small particle sizes and low polydispersity in the aqueous media, which was confirmed by CAC, DLS and TEM. Furthermore, the polyaromatic anticancer drug (doxorubicin, DOX) was selectively encapsulated in the hydrophobic core through multiple interactions with the dendrons, including π-π interactions, hydrogen bonding and hydrophobic interactions. Such multiple interactions had the merits of enhanced drug loading capacity (16.89 ± 2.41%), good stability against dilution, and excellent sustained release property. The cell viability assay presented that LP-g-G3P nanoparticles had an excellent biocompatibility both in the normal and tumor cells. Moreover, LP-g-G3P/DOX nanoparticles could be effectively internalized into the hepatoma carcinoma cells and dramatically inhibited cell proliferation. Thus, this approach paves the way to develop amphiphilic and biofunctional glycopolypeptide-based drug delivery systems.
Citation
Mohamed Wali, AR., Zhou, J., Ma, S., He, Y., Yue, D., Tang, JZ., Gu, Z. (2017) 'Tailoring the supramolecular structure of amphiphilic glycopolypeptide analogue toward liver targeted drug delivery systems', International Journal of Pharmaceutics, 525 (1) 191
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Journal article
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en
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0378-5173
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the European Commission Research and Innovation (PIRSES-GA-2011-295218)