Background: Nanoparticles are under investigation as carrier systems for anticancer drugs. The expression of efflux transporters such as the
ATP-binding cassette (
ABC) transporter ABCB1 is an important resistance mechanism in
therapy-refractory
cancer cells. Drug encapsulation into nanoparticles has been shown to bypass efflux-mediated drug resistance, but there are also conflicting results. To investigate whether easy-to-prepare nanoparticles made of well-tolerated
polymers may circumvent transporter-mediated drug efflux, we prepared
poly(lactic-co-glycolic acid) (PLGA),
polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) nanoparticles loaded with the ABCB1 substrate
doxorubicin by
solvent displacement and
emulsion diffusion approaches and assessed their anticancer efficiency in
neuroblastoma cells, including ABCB1-expressing cell lines, in comparison to
doxorubicin solution. Results: The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by
solvent displacement led to the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using
solvent displacement at pH 7 reaching 53 µg
doxorubicin/mg nanoparticle. 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 pH 7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anticancer effects. However, nanoparticle-encapsulated
doxorubicin did not display increased efficacy in ABCB1-expressing cells relative to
doxorubicin solution. Conclusion:
Doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anticancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anticancer efficacy. The design of drug-loaded nanoparticles with optimised anticancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anticancer
therapy. Further research is required to understand under which circumstances nanoparticles can be used to overcome efflux-mediated resistance in
cancer cells.