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Liposomal delivery of functional transmembrane ion channels into the cell membranes of target cells; a potential approach for the treatment of channelopathies.
Ramadan, Shahenda; Tammam, Salma N; Shetab Boushehri, Maryam A; Breitinger, Hans-Georg; Breitinger, Ulrike; Mansour, Samar; Lamprecht, Alf.
Afiliación
  • Ramadan S; Department of Pharmaceutical Technology, The German University in Cairo (GUC), Cairo, Egypt.
  • Tammam SN; Department of Pharmaceutical Technology, The German University in Cairo (GUC), Cairo, Egypt. Electronic address: Salma.nabil@guc.edu.eg.
  • Shetab Boushehri MA; Department of Pharmaceutics, University of Bonn, Bonn 53121, Germany.
  • Breitinger HG; Department of Biochemistry, The German University in Cairo (GUC), Cairo, Egypt.
  • Breitinger U; Department of Biochemistry, The German University in Cairo (GUC), Cairo, Egypt.
  • Mansour S; Department of Pharmaceutical Technology, The German University in Cairo (GUC), Cairo, Egypt.
  • Lamprecht A; Department of Pharmaceutics, University of Bonn, Bonn 53121, Germany; PEPITE EA4267, Univ. Bourgonge Franch-Comte, Besançon, France.
Int J Biol Macromol ; 153: 1080-1089, 2020 Jun 15.
Article en En | MEDLINE | ID: mdl-31756462
Defects in transmembrane ion channels underlie many disorders, commonly known as channelopathies. Current therapies are mostly symptomatic and do not treat the underlying cause. Here, we demonstrate the delivery of functional ion channels in protein form into the membrane of target cells using fusogenic proteoliposomes. The glycine receptor (GlyR) was adopted as a model channel. HEK293 cells were transfected with GlyR and GlyR-rich cell membrane fragments (CMF) were incorporated into fusogenic liposomes. Proteoliposomes were generated using 1,2-dioleoylphosphoethanolamine (DOPE) as the fusogenic lipid, lecithin, 1,2-distearoylphosphoethanolamine (DSPE), and cholesterol (Chol). Three formulations were prepared Non-fuse (2.5:0.5 Lecithin: Chol), Fuse1 (1.25:0.25:0.25:0.25) and Fuse2 (1.25:0.5:0.5:0.25 Lecithin: DOPE: DSPE: Chol). Proteoliposomes were assessed for their ability to (1) incorporate GlyR rich CMF (2) fuse with L929 fibroblast cell membrane and (3) deliver functional GlyR to these cells. All formulations were capable of integrating CMF, with Fuse2 showing highest CMF incorporation (1.2 and 1.4 folds relative to Non-fuse and Fuse1 respectively). All liposomes showed ability to fuse with the fibroblast cell membrane, with Fuse2 showing highest fusion. Patch-clamp analysis demonstrated successful delivery of functional GlyR into the fibroblast cell membrane. Thus, proof of principle was established for the use of liposomes to deliver functional ion channels to living cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Celular / Receptores de Glicina / Canalopatías Límite: Humans Idioma: En Revista: Int J Biol Macromol Año: 2020 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Celular / Receptores de Glicina / Canalopatías Límite: Humans Idioma: En Revista: Int J Biol Macromol Año: 2020 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos