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

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 < 0.05). Visualized by SPECT imaging urinary excretion represented the major pathway of elimination for both NP-formulations. In conclusion, this study provides data indicating a positive influence of PEG-derivatization on the biodistribution and pharmacokinetics of Proticles. These results form the basis for further developments as drug delivery and active drug targeting devices.