Development of PLGA nanoparticles for sustained release of a connexin43 mimetic peptide to target glioblastoma cells.

Autor: Roberts R; Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA., Smyth JW; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA; Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA., Will J; Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA., Roberts P; Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA., Grek CL; FirstString Research, Inc., Mount Pleasant, SC, USA., Ghatnekar GS; FirstString Research, Inc., Mount Pleasant, SC, USA., Sheng Z; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA; Faculty of Health Science, Virginia Tech, Blacksburg, VA, USA; Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA., Gourdie RG; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA; Faculty of Health Science, Virginia Tech, Blacksburg, VA, USA; Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, VA, USA; Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA; Center for Heart and Regenerative Medicine Research, Roanoke, VA, USA., Lamouille S; Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA; Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA. Electronic address: lamouils@vtc.vt.edu., Foster EJ; Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA. Electronic address: johanf@vt.edu.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2020 Mar; Vol. 108, pp. 110191. Date of Electronic Publication: 2019 Sep 12.
DOI: 10.1016/j.msec.2019.110191
Abstrakt: Effective therapeutic delivery of peptide and protein drugs is challenged by short in vivo half-lives due to rapid degradation. Sustained release formulations of αCT1, a 25 amino acid peptide drug, would afford lower dosing frequency in indications that require long term treatment, such as chronic wounds and cancers. In this study, rhodamine B (RhB) was used as a model drug to develop and optimize a double emulsion-solvent evaporation method of poly(lactic-co-glycolic acid) (PLGA) nanoparticle synthesis. Encapsulation of αCT1 in these nanoparticles (NPs) resulted in a sustained in vitro release profile over three weeks, characterized by an initial burst release of approximately 50% of total encapsulated drug over the first three days followed by sustained release over the remaining two and a half weeks. NP uptake by glioblastoma stem cells was through endocytosis and RhB and αCT1 were observed in cells after at least 4 days.
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Databáze: MEDLINE