A Novel Ph-Sensitive Nanocomposite Based on Graphene Oxide for Improving Doxorubicin Release Publisher Pubmed



Kachousangi MJ^{1, 2} ; Shadboorestan A³ ; Shamsian A^{1, 2} ; Amini M⁴ ; Atyabi F^{1, 2} ; Ghahremani MH^{1, 5} Show Affiliations
Source: Current Drug Delivery Published:2024

Abstract

Background: Doxorubicin (DOX) as a chemotherapeutic drug has been widely used for treatment of cancer but because of adverse side effects of this drug, different drug delivery systems have been tested. One of them has been immobilization of DOX on the graphene oxide (GO) sheets through non-covalent interactions (GO-DOX) with high efficiency however the release was very low and slow due to strong forces between DOX and GO. Objective: The aim of this research was to increase the release of DOX and this goal was achieved through the covalent binding of DOX to the GO-poly(ethyleneimine) 2KDa conjugate. Methods: A novel nanocarrier for delivering DOX was fabricated using GO as a basic plane for conjugating and assembling other compounds. DOX was attached to GO-poly(ethyleneimine) 2KDa conjugate via a linker containing hydrazide bond. Drug loading and release was investigated at pH 7.5 and pH 5.5. Cytotoxicity was determined by MTT on MCF7 cells and compared with previous nanocarrier. Results: The fabrication of the nanocarrier and the covalent attachment of DOX to the nanocarrier were confirmed through FT-IR spectroscopy. The capacity of nanocarrier to load drug was as high as 383%. 96% of initial drug was loaded in the nanocarrier. The weight percentage of the drug in the nanocarrierdrug conjugate was 79%. Release of drug at pH 5.5 was two times more than release at pH 7.5 and this evidence supports conjugation of DOX to nanocarrier through hydrazide bond and pH-sensitivity of related bond. Because of the reliable results, ease of operation, safety and high reproducibility, MTT was chosen to evaluate the cytotoxicity of samples. Nanocarrier didn’t show significant toxicity even at high concentrations. IC50 value for chemically-bound DOX to hydrazide-containing GO nanocomposite was 9.5 µg/ml whereas the IC50 value for GO-DOX was 39 µg/ml after 72 h. Loading of DOX via hydrazide bond was as low as 4% versus near 75% physical loading of drug while hydrazide bondcontaining nanocomposite was 4 to 6 fold more toxic than GO-DOX. Conclusion: Based on the obtained data, the covalent attachment of DOX to the nanocarrier through hydrazide linkers was an interesting idea that increased drug release and toxicity despite much lower percentage of covalent attachment compared to non-covalent immobilization. As could be concluded from this study, nanocarriers based on hydrazide bond could be a good candidate for drug delivery. © 2024 Bentham Science Publishers.