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Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

S. Pieper, H. Onafuye, D. Mulac, View ORCID ProfileJindrich Cinatl jr., View ORCID ProfileMark N. Wass, View ORCID ProfileM. Michaelis, K. Langer
doi: https://doi.org/10.1101/403923
S. Pieper
1Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, D-48149 Münster, Germany
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H. Onafuye
2Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom
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D. Mulac
1Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, D-48149 Münster, Germany
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Jindrich Cinatl jr.
3Institute for Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany
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  • ORCID record for Jindrich Cinatl jr.
Mark N. Wass
2Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom
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M. Michaelis
2Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom
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  • For correspondence: m.michaelis@kent.ac.uk k.langer@uni-muenster.de
K. Langer
1Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, D-48149 Münster, Germany
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  • For correspondence: m.michaelis@kent.ac.uk k.langer@uni-muenster.de
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Abstract

Nanoparticles are under investigation as carrier systems for anti-cancer drugs. They have been shown to accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect, to reduce toxicity to non-target tissues, and to protect drugs from preliminary inactivation. However, nanoparticle preparations are not commonly compared for their anti-cancer effects at the cellular level. Here, we prepared doxorubicin-loaded nanoparticles based on poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) by solvent displacement and emulsion diffusion approaches. The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement resulted in the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH7 reaching 53 µg doxorubicin/mg nanoparticle. In addition, these PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anti-cancer effects. In conclusion, doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anti-cancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anti-cancer efficacy. The design of drug-loaded nanoparticles with optimised anti-cancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anti-cancer therapy.

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Posted August 29, 2018.
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Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity
S. Pieper, H. Onafuye, D. Mulac, Jindrich Cinatl jr., Mark N. Wass, M. Michaelis, K. Langer
bioRxiv 403923; doi: https://doi.org/10.1101/403923
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Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity
S. Pieper, H. Onafuye, D. Mulac, Jindrich Cinatl jr., Mark N. Wass, M. Michaelis, K. Langer
bioRxiv 403923; doi: https://doi.org/10.1101/403923

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