title: Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro.
abstract: Cardio-vascular diseases are the main cause of death, emphasizing the need to improve patient treatment and survival. One therapeutic approach is a liposome-based drug carrier system specifically targeting constricted arteries. The recently discovered mechano-sensitive liposomes use hemodynamic shear-stress differences between healthy and constricted blood vessels as trigger for drug release. Liposomes are promising delivery containers but are being recognized as foreign by the immune system. Complement activation as essential factor of the recognition leads to adverse effects. Here, we tested complement activation by liposomes formulated from the artificial phospholipid Pad-PC-Pad in vitro. Surprisingly no complement activation was detected in human sera and porcine plasma. In in vivo experiments with three pigs, neither anaphylactic reactions nor other significant hemodynamic changes were observed even at comparably high liposome doses. The pilot study holds promise for an absence of complement-mediated adverse effects of Pad-PC-Pad liposomes in human.
  
  
  BACKGROUND
  A lot of research has been done on new treatment for cardiovascular diseases. Liposome-based carrier systems have also shown promises. In this article, the authors studied the potential risks of complement activation by liposomes in in-vivo experiments. The absence of complement activation by Pad-PC-Pad liposomes may indicate its use in humans.
authors.affiliation: Biomaterials Science Center, University of Basel, Allschwil, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Bugna
authors.affiliation: Biomaterials Science Center, University of Basel, Allschwil, Switzerland.
authors.forename: Marzia
authors.initials: M
authors.lastname: Buscema
authors.affiliation: Biomaterials Science Center, University of Basel, Allschwil, Switzerland.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Matviykiv
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Urbanics
authors.affiliation: Department of Chemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Meszaros
authors.affiliation: Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Szebeni
authors.affiliation: Department of Chemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zumbuehl
authors.affiliation: Cardiology Division, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Till
authors.initials: T
authors.lastname: Saxer
authors.affiliation: Biomaterials Science Center, University of Basel, Allschwil, Switzerland. Electronic address: bert.mueller@unibas.ch.
authors.forename: Bert
authors.initials: B
authors.lastname: Müller
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000009:adverse effects* / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D010743:Phospholipids / Q000009:adverse effects* / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D013552:Swine
chemical_list: C577072:1,3-dipalmitamidopropan-2-yl 2-(trimethylammonio)ethyl phosphate; D008081:Liposomes; D010743:Phospholipids; D003165:Complement System Proteins
keywords: CARPA; Pad-PC-Pad; Physical trigger; Pig study; Shear sensitive nano-container