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

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.