International Journal of Nanomedicine (Jan 2019)
The impact of camptothecin-encapsulated poly(lactic-co-glycolic acid) nanoparticles on the activity of cytochrome P450 in vitro
Abstract
Hanmei Bao, Qing Zhang, Zhao Yan Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 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: camptothecin, cytochrome P450, nanoparticle, drug delivery
