Synthesis and characterization of a novel, pH-responsive sustained release nanocarrier using polyethylene glycol, graphene oxide, and natural silk fibroin protein by a green nano emulsification method to enhance cancer treatment

• Published in: International journal of biological macromolecules 2023-01, Vol.226, p.1100-1115
• Main Authors: Jeshvaghani, Parisa Aarabi, Pourmadadi, Mehrab, Yazdian, Fatemeh, Rashedi, Hamid, Khoshmaram, Keyvan, Nigjeh, Mona Navaei
• Format: Article
• Language: English
• Subjects: Cancer treatment; Delayed-Action Preparations - pharmacology; Doxorubicin; Drug Carriers - chemistry; Fibroins; Graphene oxide; Graphite - chemistry; Humans; Hydrogen-Ion Concentration; Neoplasms; pH-sensitivity; Polyethylene Glycols - chemistry; Silk fibroin; Sustained release
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.11.226

In this study, for the first time, by employing a simple and efficient double nano-emulsification method and using sweet almond oil as the organic phase, polyethylene glycol (PEG)/graphene oxide (GO)/silk fibroin (SF) hydrogel-nanocomposite was synthesized. The aim of the research was to fabricate a biocompatible targeted pH-sensitive sustained release carrier, improve the drug loading capacity and enhance the anticancer effect of doxorubicin (DOX) drug. The obtained values for the entrapment (%EE) and loading efficacy (%LE) were 87.75 ± 0.7 % and 46 ± 1 %, respectively, and these high values were due to the use of GO with a large specific surface area and the electrostatic interaction between the drug and SF. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses confirmed the presence of all the components in the nanocomposite and the suitable interaction between them. Based on the results of dynamic light scattering analysis (DLS) and zeta potential analysis, the mean size of the carrier particles and its surface charge were 293.7 nm and −102.9 mV, respectively. The high negative charge was caused by the presence of hydroxyl groups in GO and SF and it caused proper stability of the nanocomposite. The spherical core-shell structure with its homogeneous surface was also observed in the field emission scanning electron microscopy (FE-SEM) image. The cumulative release percentage of the nanocarrier reached 95.75 after 96 h and it is higher in the acidic environment at all times. The results of fitting the release data to the kinetic models suggested that the mechanism of release was dissolution-controlled anomalous at pH 7.4 and diffusion-controlled anomalous at pH 5.4. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry showed an increase in toxicity on MCF-7 cells and improved apoptotic cell death compared to the free drug. Consequently, the findings of this research introduced and confirmed PEG/GO/SF nanocomposite as an attractive novel drug delivery system for pH-sensitive and sustained delivery of chemotherapeutic agents in biomedicine. •First modification of PEG/GO with natural SF protein and double nanoemulsion encapsulation of PEG/GO/SF/DOX carrier•Using Natural sweet almond oil instead of paraffin oil to make nanoemulsion•Providing a sustained and pH-sensitive release for DOX and increasing its bioavailability•Increased loading and entrapment efficiency of DOX