The impact of camptothecin-encapsulated poly(lactic-co-glycolic acid) nanoparticles on the activity of cytochrome P450 in vitro
Open Access
- 1 January 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in International Journal of Nanomedicine
- Vol. ume 14, 383-391
- https://doi.org/10.2147/ijn.s188984
Abstract
Background: Poly(lactic-co-glycolic acid) (PLGA) has emerged as a promising anticancer drug delivery scaffold. Camptothecin (CPT) has been fabricated into a variety of nano-sized formulations to improve drug action. We report an experimental study on the effect of CPT-encapsulated PLGA (PLGA-CPT) nanoparticles (NPs) on drug-metabolizing cytochrome P450 enzyme, CYP3A4. Materials and methods: PLGA-CPT NPs were prepared by a single emulsion–solvent evaporation method. Results: Transmission electron micrography showed that the NPs had a round and regular shape with a mean diameter of 94.6±5.7 nm. An in vitro drug release study showed that CPT was continuously released for 48 h. PLGA-CPT NPs showed greater cytotoxic effects on the HepG2 cell line compared with an equal dose of free CPT. Correlation with 4-h uptake data suggested that this was due to a higher cellular uptake amount of CPT from PLGA-CPT NPs than from free CPT. PLGA-CPT NPs tended to inhibit CYP3A4 activity isolated from HepG2 cells. However, PLGA-CPT NPs had no effect on the CYP3A4 mRNA levels. Furthermore, the interaction between PLGA-CPT NPs and CYP3A4 was investigated by ultraviolet–visible absorption spectroscopy and fluorescence spectroscopy. Conclusion: Taken together, the results demonstrate that CYP3A4 may be inhibited by PLGA-CPT NPs and interference with biotransformation should be considered when using NPs as drug delivery vesicles.Keywords
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