Structure-Activity Relationship of Mono-Ion Complexes for Plasmid DNA Delivery by Muscular Injection

• Główni autorzy: Amika Mori (Autor), Yuki Kobayashi (Autor), Kei Nirasawa (Autor), Yoichi Negishi (Autor), Shoichiro Asayama (Autor)
• Format: Książka
• Wydane: MDPI AG, 2021-01-01T00:00:00Z.
• Hasła przedmiotowe: article
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Streszczenie

The structure-activity relationship of mono-ion complexes (MICs) for plasmid DNA (pDNA) delivery by muscular injection is demonstrated. MICs were formed between pDNA and monocationic poly(ethylene glycol) (PEG) macromolecules. As monocationic PEGs, the ω-amide-pentylimidazolium (APe-Im) end-modified PEGs with a stable amide (Am) and hydrolytic ester (Es) bond, that is, APe-Im-Am-PEG and APe-Im-Es-PEG, respectively, are synthesized. The difference between the APe-Im-Am-PEG and APe-Im-Es-PEG was only a spacer structure between a terminal cation and a PEG chain. The resulting pDNA MICs with APe-Im-Am-PEG at a charge ratio (+/−) of 32 or 64 were more stable than those with APe-Im-Es-PEG in the presence of serum proteins. The highest gene expression by muscular injection was achieved using the APe-Im-Am-PEG/pDNA MIC at a charge ratio (+/−) of 32 with a smaller particle diameter of approximately 50 nm, as compared to that charge ratio of 64. Consequently, the pDNA MIC with the monocationic PEG with a stable amide spacer, as compared to a hydrolytic ester spacer, is considered to be suitable for the highest gene expression by muscular injection.

Deskrypcja

10.3390/pharmaceutics13010078
1999-4923