TY  - JOUR
A1  - Pieper, Sebastian
A1  - Onafuye, Hannah
A1  - Mulac, Dennis
A1  - Cinatl, Jindrich
A1  - Wass, Mark N.
A1  - Michaelis, Martin
A1  - Langer, Klaus
T1  - Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity
T2  - bioRxiv beta
N2  - 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.
KW  - Nanoparticles
KW  - doxorubicin
KW  - poly(lactic-co-glycolic acid) (PLGA)
KW  - polylactic acid (PLA)
KW  - PEGylated PLGA (PLGA-PEG)
KW  - emulsion diffusion
KW  - solvent displacement
KW  - drug release
KW  - cancer
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53412
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-534120
N1  - The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
N1  - Endgültige Version erschienen in: Beilstein journal of nanotechnology, 10.2019, S. 2062–2072, doi:10.3762/bjnano.10.201
VL  - 2018
SP  - 1
EP  - 33
PB  - Cold Spring Harbor Laboratory, NY
CY  - Cold Spring Harbor
ER  -