Fe3O4 @ PLGA-PEG Nanocomposite for Improved Delivery of Methotrexate in Cancer Treatment

摘要

abstract_textpMagnetic Fe3O4 nanoparticles are gaining significance in drug delivery applications owing to their targeting capability. Surface modification of amphiphilic block polymers by Fe3O4 nanoparticles increases their properties. In this study, Fe3O4 @ PLGA-PEG nanocomposite is prepared by double emulsion (w/o/w) method. A shift in the 2 values for the composite in XRD attributes to interaction between Fe3O4 and PLGA-PEG. Also, a shift in the Fe-O band in the FTIR spectrum of Fe3O4@PLGA-PEG from 578 cm(-1) to 510 cm(-1) confirms the formation of nanocomposite. Surface morphology of the prepared nanocomposite is analyzed by TEM and AFM. Decrease in agglomeration due to electrostatic repulsion between the polymer chains and magnetic particles is observed while an increased surface area (61.0 nm) confirms the formation of the nanocomposite. To determine the effectiveness of the prepared magnetically modified nanoparticles, methotrexate (anticancer drug) is encapsulated into the nanocomposite. High entrapment efficiency of 95 is observed when polymer:drug is 1:1. The in-vitro release profile shows that pH of release medium plays a significant role. At physiological pH of 7.3 there is only 15 methotrexate release while nearly 86 of methotrexate release is observed at acidic pH of 4.6 over 72 h. Korsemeyer-Peppas model of drug release (R-2-0.9868) represents swelling controlled release of methotrexate. Further, the cytotoxic cell viability assay on SK-BR-3 (breast adinocarcinoma) cells showed that methotrexate loaded onto the nanocomposite showed higher cell viability as compared to free methotrexate after 96 h of incubation. The fluorescent cell imaging also showed that methotrexate released slowly from the nanoparticles and diffused into the nucleus without losing its cytotoxic effect on the cancer cells. Based on these properties of the magnetically modified PLGA-PEG nanoparticles they can be used as targeting drug delivery agents in treatment of cancer therapy./p/abstract_text