κ-carrageenan coated magnetic hydroxypropyl methylcellulose/chitosan nanoparticles as a pH-sensitive nanocarrier for efficient methotrexate release.

Recently, the cross-linking of polymer-carriers for controlled drug release to target sites has attracted more attention from researchers. Hence, in the present study, mHPMC-Chito/κ-Car nanoparticles (NPs) were designed through the cross-linking of magnetic hydroxypropyl methylcellulose (mHPMC)/chitosan (Chito) with κ-carrageenan (κ-Car) to be used for controlled and targeted methotrexate (MTX) release. The chemical structure of the designed mHPMC-Chito/κ-Car NPs was assessed through various methods, including FE-SEM/EDS, TGA, FT-IR, TEM, zeta potential, and XRD. The size of the cross-linked mHPMC-Chito2/κ-Car nanoparticles was obtained at about 50 ± 5 nm. The MTX encapsulation efficiency (EE%) for MTX@mHPMC-Chito1/κ-Car, MTX@mHPMC-Chito2/κ-Car, and MTX@mHPMC-Chito3/κ-Car NPs was obtained as about 71.8 %, 85.3 %, and 89.4 %, respectively. The in vitro drug release showed a low release rate of MTX at pH 7.4 compared to pH 5.5, which confirms the pH-sensitive behavior of the prepared MTX@mHPMC-Chito/κ-Car NPs. In addition, the biocompatibility of the mHPMC-Chito2/κ-Car NPs was proved by in vitro cell viability assay using the MTT assay. According to the obtained results, the higher cytotoxicity of MTX@mHPMC-Chito2/κ-Car was observed against MDA-MB 231 breast cancer cells, which could be related to the controlled release of the MTX from the NPs. The in vitro hemolysis, antioxidant, and enzymatic degradation studies indicated that the synthesized NPs as anticancer drug delivery systems have good blood compatibility, antioxidant, and biodegradability properties. Therefore, the designed mHPMC-Chito/κ-Car NPs could be potentially used in biomedicine applications.