Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: in vitro anti-proliferative and anti-invasive activity in glioblastoma. Issue 53 (30th September 2019)

• Record Type: Journal Article
• Authors: Alshaer, Walhan; Zraikat, Manar; Amer, Amer; Nsairat, Hamdi; Lafi, Zainab; Alqudah, Dana A.; Al Qadi, Enas; Alsheleh, Tasneem; Odeh, Fadwa; Alkaraki, Arwa; Zihlif, Malek; Bustanji, Yasser; Fattal, Elias; Awidi, Abdalla
• Is Part Of: RSC advances. Volume 9:Issue 53(2019)
• Page Start: 30976
• Page End: 30988
• Publication Date: 2019-09-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9ra05636j
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Echinomycin, a DNA bis-intercalator peptide antibiotic, was complexed with γCD and loaded into PEGylated liposomes. The liposomes encapsulating echinomycin showed potent anti-proliferative and anti-invasive effect against U-87 MG glioblastoma cells. Abstract : Echinomycin, a DNA bis-intercalator peptide, belongs to the family of quinoxaline antibiotics. Echinomycin exhibits potent antitumor and antimicrobial activity. However, it is highly water insoluble and suffers from low bioavailability and unwanted side effects. Therefore, developing new formulations and delivery systems that can enhance echinomycin solubility and therapeutic potency is needed for further clinical application. In this study, echinomycin has been complexed into the hydrophobic cavity of γ-cyclodextrin (γCD) then encapsulated into PEGylated liposomes. The anti-proliferative and anti-invasive effect has been evaluated against U-87 MG glioblastoma cells. Echinomycin-in-γCD inclusion complexes have been characterized by phase solubility assay, TLC, and 1 H-NMR. The echinomycin-in-γCD inclusion complexes have been loaded into liposomes using a thin film hydration method to end up with echinomycin-in-γCD-in-liposomes. Drug-loaded liposomes were able to inhibit cell proliferation with IC50 of 1.0 nM. Moreover, echinomycin-in-γCD-in-liposomes were found to inhibit the invasion of U-87 MG cells using the spheroid gel invasion assay. In conclusion, the current work describes for the first time γCD-echinomycin complexes and their encapsulation into PEGylated liposomes.