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

Rose Roberts; James W Smyth; John Will; Payton Roberts; Christina L Grek; Gautam S Ghatnekar; Zhi Sheng; Robert G Gourdie; Samy Lamouille; E Johan Foster

doi:10.1016/j.msec.2019.110191

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

Mater Sci Eng C Mater Biol Appl. 2020 Mar:108:110191. doi: 10.1016/j.msec.2019.110191. Epub 2019 Sep 12.

Authors

Affiliations

¹ Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA.
² 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.
³ FirstString Research, Inc., Mount Pleasant, SC, USA.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ Virginia Tech, Macromolecule Innovation Institute and Materials Science and Engineering Department, Blacksburg, VA, USA. Electronic address: johanf@vt.edu.

PMID: 31923988
DOI: 10.1016/j.msec.2019.110191

Abstract

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.

Keywords: Cancer stem cell; Drug release; Glioblastoma; αCT1 peptide.

MeSH terms

Biomimetic Materials* / chemistry
Biomimetic Materials* / pharmacology
Cell Line, Tumor
Connexin 43* / chemistry
Connexin 43* / pharmacology
Delayed-Action Preparations / chemistry
Delayed-Action Preparations / pharmacology
Glioblastoma* / drug therapy
Glioblastoma* / metabolism
Humans
Nanoparticles* / chemistry
Nanoparticles* / therapeutic use
Peptides* / chemistry
Peptides* / pharmacology
Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry
Polylactic Acid-Polyglycolic Acid Copolymer* / pharmacology

Substances

Connexin 43
Delayed-Action Preparations
Peptides
Polylactic Acid-Polyglycolic Acid Copolymer

Grants and funding

R21 CA216768/CA/NCI NIH HHS/United States