Comparison of PEGylated and non-PEGylated proticles: An in vitro and in vivo study.
Eur J Pharm Sci
; 139: 105063, 2019 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-31487537
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⯱â¯0.01 % ID/g 1â¯h p.i.; 111In-proticles 0.06⯱â¯0.01 % ID/g 1â¯h p.i.; pâ¯<â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligonucleotides
/
Polyethylene Glycols
/
Protamines
/
Nanoparticles
Limits:
Animals
Language:
En
Journal:
Eur J Pharm Sci
Journal subject:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
Austria