Cited by 72Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsDendrimers and Hyperbranched Polymers

Correlation between drug loading content and biological activity: the complexity demonstrated in paclitaxel-loaded glycopolymer micelle system

Cao, Cheng, Zhao, Jiacheng, Lu, Mingxia, Garvey, Christopher J., Stenzel, Martina H.·2019·Biomacromolecules

Abstract

Drug delivery carriers are now widely established because they can increase the therapeutic efficiency of drugs. In general, the aim in this field is to create effective carriers that have large amounts of drugs loaded to minimize drug carrier material that needs to be disposed of. However, there has been little attention so far in the literature on the effect of the amount of loaded drugs on the biological activity. In this paper, we are trying to answer the question of how the drug-loading content will affect the in vitro activity. We use two methods to load paclitaxel (PTX) into micelles based on the glycopolymer, poly(1- O -methacryloyl-β- d -fructopyranose)- block -poly(methyl methacylate) (Poly(1- O -MAFru) 35 - b -PMMA 145 ). In the one-step method, the drug is loaded into the particles during the self-assembly process. However, the size of nanoparticle increased with the PTX content from 26 to 50 nm, triggering enhanced cellular uptake by MCF-7 and MDA-MB-231, which was caused by changes in diameter size and not by changes in drug concentration. To keep the nanoparticle size constant, preformed micelles were loaded with PTX (two-step process). The increasing amount of loaded drug led to decreased cellular uptake and reduced cytotoxicity by the cancer cell lines. Small-angle neutron scattering and small-angle X-ray scattering, supported by transmission electron microscopy and dynamic light scattering, exposed the PTX location in the shell. This caused shrinkage of the shell and lower levels of shell hydration, resulting in lower cellular uptake and lower cytotoxicity. Upon the release of PTX, the shell regained its original level of hydration. We could show that because drug loading causes morphology changes, in either the shell or the size, it is impossible to separate the parameters that will influence the biological activity. Although the same phenomenon may not apply to every drug delivery system, it needs to be considered that except for the well-known parameters that affect cell uptake—size, shape, surface chemistry, type of nanoparticle, and presence of bioactive groups—the amount of loaded drugs might change the physicochemical parameters of the nanoparticle and thus the in vitro and potentially the in vivo outcomes.

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Crossref · 10.1021/acs.biomac.8b01707

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Authors
Cao, C., Zhao, J., Lu, M., Garvey, C. J., & Stenzel, M. H.
Affiliations
  • Australian Nuclear Science and Technology Organisation (AU)
  • UNSW Sydney (AU)
Corresponding author
  • Garvey, Christopher J.
  • Stenzel, Martina H.
Venue
Biomacromolecules
Published
2019-02-15
Volume
20
Issue
4
Pages
1545-1554
ISSN
  • 1525-7797 (ISSN-L)
  • 1526-4602
OpenAlex
W2913876499
Cited by
72
References
51
Citations by year
2026: 2 · 2025: 10 · 2024: 7 · 2023: 16 · 2022: 13 · 2021: 14 · 2020: 8 · 2019: 2
FWCI
2.62
Type
journal article
Language
en
Open access
closed
Locations
  • Biomacromolecules (publishedVersion)
  • PubMed (publishedVersion)
Funders
Australian Research Council (DP160101172)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
paclitaxel, nanoparticle size, cellular uptake, cytotoxicity, drug release, MCF-7 cells, MDA-MB-231 cells, breast cancer, nanoparticle morphology
MeSH terms
Drug Carriers, Glycoconjugates, Humans, Micelles, Particle Size, Paclitaxel, Nanoparticles, MCF-7 Cells

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