Interactions of phosphorus-containing dendrimers with liposomes Dominika Wrobel a, ⁎, Maksim Ionov a , Konstantinos Gardikis b , Costas Demetzos b , Jean-Pierre Majoral c , Bartlomiej Palecz d , Barbara Klajnert a , Maria Bryszewska a a Department of General Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland b Department of Pharmaceutical Technology, School of Pharmacy, Greece c Laboratoire de Chimie de Coordination CNRS, Toulouse, France d Department of Physical Chemistry, University of Lodz, Lodz, Poland abstract article info Article history: Received 22 July 2010 Received in revised form 18 November 2010 Accepted 19 November 2010 Available online 1 December 2010 Keywords: Cationic phosphorus-containing dendrimers Liposomes DSC Anisotropy Membrane fluidity The influence of cationic phosphorus-containing dendrimers generation 3 and 4 on model DMPC or DPPC lipid membranes was studied. Measurements of fluorescence anisotropy and differential scanning calorimetry (DSC) were applied to assess changes in lipid bilayer parameters, including fluidity, anisotropy, and phase- transition temperature. Interaction with both hydrophobic and hydrophilic regions of the bilayer was followed by these methods. Dendrimers of both generations influence lipid bilayers by decreasing membrane fluidity. The results suggest that dendrimers can interact both with the hydrophobic part and the polar head- group region of the phospholipid bilayer. Higher generation dendrimers interact more strongly with model membranes, and the concentration, as well as the generation, is of similar importance. © 2010 Elsevier B.V. All rights reserved. 1. Introduction The history of dendrimers started about 30 years ago, and today there are many kinds that all share a similar structure. Dendrimers are different from traditional linear polymers. Generally, their construc- tion consists of branches emanating from a core, along with a well- defined number of active groups on their surface. Their unique structural features hold out promise of many applications in the fields of nanoelectronics and (electro)chemical (bio)sensors, or they can be used as carriers of active substances, anti-prion agents, insulating materials, and transfecting agents [1–9]. A relatively new promising class contains cationic phosphorus-containing dendrimers. These molecules have a hydrophilic surface and a hydrophobic backbone that allows for very efficient membrane penetration. They have protonated terminary amine end groups on their surfaces and their number is related to their generation [10]. How these carriers behave during interaction with biological membranes is worth considering when synthesizing new drug carriers. Many drugs have not been effective due to their inability to reach the appropriate tissue. It is difficult to design and develop drug carriers that behave as biocolloidal systems in the body. To use any new materials as drug carriers, one needs to understand how they interact with biological structures like cell membranes. Biological membranes are very complicated structures so it is difficult to understand their complexed interactions with dendrimers. To simplify the experimental model, lipid membranes were used for these studies instead of biological membranes. Lipid vesicles are simple structures that provide a lot of information about interactions between drugs and biological mem- branes. When interactions between model lipid membranes and dendrimers are examined, conclusions can be drawn about biological processes such as membrane fusion and transport of this new material for drug or gene delivery [11]. Results of interactions between cationic phosphorus-containing dendrimers of generation 3 (G3) and generation 4 (G4) with model lipid membranes composed of DMPC or DPPC phospholipids have been explored. Because of water solubility most of the potential applications of phosphorus-containing dendrimers are related to biology. Phospho- rus dendrimers are more stable then PAMAM dendrimers but less than PPI dendrimers. They possess hydrophobic interior and the hydrophilic end groups. The number of cationic end groups, molecular weights, and the structures of cationic phosphorus-containing dendrimers of generations 3 (C 624 H 1104 N 183 Cl 48 O 42 P 45 S 42 ) and 4 (C 1296 H 2256 N 375 Cl 96 O 90 P 93 S 90 ) are shown in Fig. 1 [10,12]. 2. Materials and methods 2.1. Materials Lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC); 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); fluorescent probes: 1,6-diphenyl-1,3,5-hexatriene (DPH); N,N,N-trimethyl-4-(6- Biochimica et Biophysica Acta 1811 (2011) 221–226 ⁎ Corresponding author. Tel.: +48 42 6354144; fax: +48 42 6354474. E-mail address: domwro@biol.uni.lodz.pl (D. Wrobel). 1388-1981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbalip.2010.11.007 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbalip