Design of slow-release methotrexate drug delivery system using PHBV magnetic nanoparticles and evaluation of its cytotoxicity

Abstract

Methotrexate (MTX) is a folic acid antagonist that is useful in the treatment of a variety of cancers. However, due to its dose-dependent complications, drug resistance, narrow therapeutic index, poor bioavailability, and low water solubility, in cancer chemotherapy, MTX has a limited role. To improve drug delivery to the target tissue, reduce MTX cytotoxicity, and increase its efficiency, MTX–loaded magnetic nanoparticles (MNPs) and methanolic extract of helichrysum graveolens (M. Bieb.) sweet were prepared. MNPs were made utilizing poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a double emulsion-solvent evaporation method and optimized using Box–Behnken design (BBD) and response surface methodology (RSM). The optimized PHBV MNPs were included of spherical particles with a mean size of about 90 nm, encapsulation efficiency of 84.8 ± 0.02% and drug release efficiency of 91.8 ± 0.1% during 96 h. The infrared spectrum confirmed the bond between the drug, extract and magnetite functional groups with PHBV nanoparticles. The magnetic curve showed that the synthesized PHBV MNPs have superparamagnetic properties and their saturation magnetization (MS) is equal to 44.19 emu.g−1. energy dispersive x-ray spectroscopy (EDS) and elemental mapping confirmed the presence of elements in the nanocarrier and their uniform distribution at the sample level, respectively. the in vitro cell toxicity studies showed the blank PHBV NPs did not impress cell viability after 72 h which indicated significant biocompatibility of PHBV nanoparticles. While, the PHBV-MTX-herb magnetic nanoparticles showed higher cytotoxicity than free MTX on cancer cells. Apoptosis analysis was performed by flow cytometry. Induced apoptosis was dependent on the duration and rate of drug release. The findings also revealed that PHBV nanoparticles could encapsulate MTX without changing its properties. also, they are a promising carrier for the Prescription of hydrophobic drugs for treatment of cancer.