Details

Autor(en) / Beteiligte

• Kannaka, Kento
• Sano, Kohei
• Hagimori, Masayori
• Yamasaki, Toshihide
• Munekane, Masayuki
• Mukai, Takahiro

Titel

Synthesis of an amphiphilic tetrazine derivative and its application as a liposomal component to accelerate release of encapsulated drugs

Ist Teil von

• Bioorganic & medicinal chemistry, 2019-08, Vol.27 (16), p.3613-3618

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• [Display omitted] •An amphiphilic tetrazine derivative (Compound 1) was newly synthesized.•The 1 introduced into liposome membranes was chemically reacted with 2-norbornene.•The chemical reaction increased the membrane fluidity of liposomes.•The augmentation of drug release from liposomes was shown after chemical reaction.•Liposomes containing 1 are promising for controlled drug release by chemical reaction. Tetrazine irreversibly reacts with dienophiles, and its derivatives find wide applications in the fields of biochemistry and biophysics. We have synthesized an amphiphilic tetrazine derivative (2-hexadecyl-N-(6-(6-(pyridin-2-yl)-1,2,4,5-tetrazine-3-yl)pyridin-3-yl)octadecanamide; 1), which has a hydrophilic tetrazine structure and hydrophobic alkyl chains. Liposomes composed of compound 1 and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) (PTz-liposome) were prepared. In search of a new drug delivery system (DDS), we investigated the viability of inverse electron-demand Diels-Alder, a reaction between tetrazine and 2-norbornene, on the surface of the liposomes to change membrane fluidity and promote spatial and temporal controlled release of the encapsulated drugs. Compound 1 was synthesized with a yield of 71%. MS analysis after incubation of 2-norbornene with PTz-liposome revealed the binding of 2-norbornene to tetrazine. Indium-111-labeled diethylenetriaminepentaacetic acid (111In-DTPA) was encapsulated inside PTz-liposome to evaluate the leakage of free 111In-DTPA from the liposomes quantitatively. After 24 h of adding 2-norbornene, the release percentage for PTz-liposome was significantly higher than that for the control liposome (without tetrazine structure). Furthermore, the membrane fluidity of the PTz-liposome was increased by adding 2-norbornene. These results suggested that the combination of dienophile and liposome containing a newly synthesized tetrazine derivative can be used as a controlled release DDS carrier.