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Assessment of pH Responsive Delivery of Methotrexate Based on PHEMA-st-PEG-DA Nanohydrogels
Javad Farzanfar,Fatemeh Farjadian,Amir Roointan,Soliman Mohammadi-Samani,Lobat Tayebi 한국고분자학회 2021 Macromolecular Research Vol.29 No.1
Nanohydrogels (NHs) are novel and attractive carriers for various anticancer factors delivery. The objective of present study is development of a safe NH for pH responsive delivery of methotrexate (MTX). Herein, poly (hydroxyethyl methacrylate) is utilized as the main structure, which is cross-linked with poly(ethyleneglycol) diacrylate (PEG-DA) through reversible addition fragmentation chain transfer polymerization technique. After synthesis, the developed structure is characterized using different methods, including 1H NMR, FT-IR, size exclusion chromatography, transmission electron microscopy and dynamic light scattering. The results confirm successful synthesis of the NH with acceptable yield and nano scale mean size of 194 nm. Methotrexate is conjugated with the aforementioned structure through pH responsive esteric bond. The efficiency of the prepared NH in loading and release of the anticancer drug, methotrexate, is tested. The developed NH shows great potential in methotrexate loading, as well as a faster release rate of methotrexate in acidic pH. The results of in vitro toxicity assessment on MCF-7 as a breast cancer cell line reveal an improved cytotoxicity induction by the methotrexate loaded particles when compared with the free MTX molecules. The suitable size (<200 nm), great potential in loading and release of the methotrexate and cytotoxicity induction in cancer cells are the reliable features of NH as an ideal anti-cancer vehicle.
Ali Dehshahri,Samira Hossaini Alhashemi,Akram Jamshidzadeh,Zahra Sabahi,Soliman Mohammadi Samani,Hossein Sadeghpour,Erfaneh Mohazabieh,Mahin Fadaei 한국고분자학회 2013 Macromolecular Research Vol.21 No.12
Interleukin-12 (IL-12) has been proposed for cancer immunotherapy due to its versatile antitumor and antiangiogenesis effects. Although cancer immunotherapy through systemic administration of IL-12 has shown antitumor effects in tumor-bearing mice, broad application of recombinant IL-12 protein has been limited by its cytotoxicity. Therefore, the use of various polycationic polymers such as polyethylenimine (PEI), polyamidoamine (PAMAM) and chitosan has been considered as an effective strategy to transfer plasmid encoding IL-12 gene into cells. In this investigation, polyplexes (polymer/pDNA complexes) were prepared using PEI, PAMAM and chitosan at different N/P ratios and their ability in transferring plasmid encoding IL-12 gene was evaluated. Furthermore,these polyplexes were characterized and compared with regarding their cytotoxicity, DNA condensation ability, particle size, zeta potential, buffering capacity and pDNA protection against enzyme degradation. The results revealed that the polyplexes formulated with 25 kDa PEI and chitosan had the highest transfection efficiencies. The highest level of IL-12 gene expression was achieved by the nanoparticles prepared by 25 kDa PEI where they could increase the level of gene expression up to 12 times compared to that of naked plasmid encoding IL-12 gene. These results suggest that 25 kDa PEI and chitosan are the best candidates for adding targeting ligands into their structures in order to create a liver targeting gene delivery system.