Comparison of PEGylated and non-PEGylated proticles: An in vitro and in vivo study

Abstract The development of so-called Proticles opens attractive possibilities for new drug delivery systems. Proticles are nanoparticles (NPs), which are formed by self-assembly of negatively charged oligonucleotides in combination with the positively charged peptide protamine. Polyethylene glycol (PEG) is a widely known pharmaceutical agent to stop particle growth and prolong circulation half-life of drug delivery systems. Therefore, two different NP formulations – one PEGylated and one non-PEGylated – were used in this work to gain information about the biological stability and half-life in circulation of Proticles. Thus, this study presents data of in vitro stability and in vivo pharmacokinetics of both, non-PEGylated and PEGylated Proticles radiolabeled with 111InCl3. The study demonstrated that successful radiolabeling of both Proticle-formulations was performed resulting in high radiochemical yields (> 85%). Furthermore, the influence of PEGylation on the in vitro stability of 111In-radiolabeled NPs was investigated. No significant difference due to PEGylation was found. Unlike in vitro results, non-PEGylated 111In-Proticles seemed to degrade faster in vivo than PEGylated 111In-proticles, resulting in significantly higher blood values (111In-PEG-proticles: 0.23 ± 0.01% ID/g 1 h p.i.; 111In-proticles: 0.06 ± 0.01% ID/g 1 h p.i.; p