Journal
PHARMACEUTICAL RESEARCH
Volume 37, Issue 9, Pages -Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-020-02899-5
Keywords
DNA polyplexes; interferon-beta1; glioblastoma; transfection; zwitterionic phosphorylcholine polymer
Funding
- School of Pharmacy from Duquesne University (DU)
- Faculty Development Fund from Duquesne University (DU)
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Purpose We tested polyplexes of a diblock polymer containing a pH-responsive, endosomolytic core (dimethylaminoethyl methacrylate and butyl methacrylate; DB) and a zwitterionic Poly (methacryloyloxyethyl phosphorylcholine) (PMPC) corona for the delivery of plasmid DNA (pDNA) to glioblastoma cells. Methods We studied the physicochemical characteristics of the DNA polyplexes such as particle hydrodynamic diameter and surface potential. Cytocompatibility of free PMPC-DB polymer and pDNA polyplexes with U-87MG and U-138MG glioma cell lines were evaluated using the ATP assay. The transfection activity of luciferase pDNA polyplexes was measured using a standard luciferase assay. Anti-proliferative, apoptotic, and cell migration inhibitory activities of PMPC-DB/Interferon-beta (IFN-beta 1) pDNA polyplexes were examined using ATP assay, flow cytometry, and wound closure assay, respectively. Results PMPC-DB copolymer condensed pDNA into nanosized polyplexes. DNA polyplexes showed particle diameters ranging from ca. 100-150 nm with narrow polydispersity indices and near electroneutral zeta potential values. PMPC-DB/Luciferase pDNA polyplexes were safe and showed an 18-fold increase in luciferase expression compared to the gold standard PEI polyplexes in U-87MG cells. PMPC-DB/IFN-beta 1 polyplexes induced apoptosis, demonstrated anti-proliferative effects, and retarded cell migration in glioblastoma cells. Conclusion The results described herein should guide the future optimization of PMPC-DB/DNA delivery systems forin vivostudies.
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