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Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery

[Image: see text] Delivery of poorly soluble anticancer drugs can be achieved by employing polymeric drug delivery systems, capable of forming stable self-assembled nanocarriers with drug encapsulated within their hydrophobic cores. Computational investigations can aid the design of efficient drug-d...

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Autores principales: Jiang, Wenjuan, Luo, Juntao, Nangia, Shikha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760677/
https://www.ncbi.nlm.nih.gov/pubmed/25532019
http://dx.doi.org/10.1021/la503949b
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author Jiang, Wenjuan
Luo, Juntao
Nangia, Shikha
author_facet Jiang, Wenjuan
Luo, Juntao
Nangia, Shikha
author_sort Jiang, Wenjuan
collection PubMed
description [Image: see text] Delivery of poorly soluble anticancer drugs can be achieved by employing polymeric drug delivery systems, capable of forming stable self-assembled nanocarriers with drug encapsulated within their hydrophobic cores. Computational investigations can aid the design of efficient drug-delivery platforms; however, simulations of nanocarrier self-assembly process are challenging due to high computational cost associated with the large system sizes (millions of atoms) and long time scales required for equilibration. In this work, we overcome this challenge by employing a multiscale computational approach in conjunction with experiments to analyze the role of the individual building blocks in the self-assembly of a highly tunable linear poly(ethylene glycol)-b-dendritic oligo(cholic acid) block copolymer called telodendrimer. The multiscale approach involved developing a coarse grained description of the telodendrimer, performing simulations over several microseconds to capture the self-assembly process, followed by reverse mapping of the coarse grained system to atomistic representation for structural analysis. Overcoming the computational bottleneck allowed us to run multiple self-assembly simulations and determine average size, drug-telodendrimer micellar stoichiometry, optimal drug loading capacity, and atomistic details such hydrogen-bonding and solvent accessible area of the nanocarrier. Computed results are in agreement with the experimental data, highlighting the success of the multiscale approach applied here.
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spelling pubmed-47606772016-02-29 Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery Jiang, Wenjuan Luo, Juntao Nangia, Shikha Langmuir [Image: see text] Delivery of poorly soluble anticancer drugs can be achieved by employing polymeric drug delivery systems, capable of forming stable self-assembled nanocarriers with drug encapsulated within their hydrophobic cores. Computational investigations can aid the design of efficient drug-delivery platforms; however, simulations of nanocarrier self-assembly process are challenging due to high computational cost associated with the large system sizes (millions of atoms) and long time scales required for equilibration. In this work, we overcome this challenge by employing a multiscale computational approach in conjunction with experiments to analyze the role of the individual building blocks in the self-assembly of a highly tunable linear poly(ethylene glycol)-b-dendritic oligo(cholic acid) block copolymer called telodendrimer. The multiscale approach involved developing a coarse grained description of the telodendrimer, performing simulations over several microseconds to capture the self-assembly process, followed by reverse mapping of the coarse grained system to atomistic representation for structural analysis. Overcoming the computational bottleneck allowed us to run multiple self-assembly simulations and determine average size, drug-telodendrimer micellar stoichiometry, optimal drug loading capacity, and atomistic details such hydrogen-bonding and solvent accessible area of the nanocarrier. Computed results are in agreement with the experimental data, highlighting the success of the multiscale approach applied here. American Chemical Society 2014-12-22 2015-04-14 /pmc/articles/PMC4760677/ /pubmed/25532019 http://dx.doi.org/10.1021/la503949b Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Jiang, Wenjuan
Luo, Juntao
Nangia, Shikha
Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title_full Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title_fullStr Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title_full_unstemmed Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title_short Multiscale Approach to Investigate Self-Assembly of Telodendrimer Based Nanocarriers for Anticancer Drug Delivery
title_sort multiscale approach to investigate self-assembly of telodendrimer based nanocarriers for anticancer drug delivery
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760677/
https://www.ncbi.nlm.nih.gov/pubmed/25532019
http://dx.doi.org/10.1021/la503949b
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AT nangiashikha multiscaleapproachtoinvestigateselfassemblyoftelodendrimerbasednanocarriersforanticancerdrugdelivery