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Chemistry and Physics of Lipids 165 (2012) 401– 407

Contents lists available at SciVerse ScienceDirect

Chemistry and Physics of Lipids

j ourna l ho me p ag e : www.elsev ier .com/ locate /chemphys l ip

ationic carbosilane dendrimers–lipid membrane interactions

ominika Wrobela,∗, Arkadiusz Kłysb, Maksim Ionova, Pavol Vitovicc, Iveta Waczulikowac,ibor Hianikc, Rafael Gomez-Ramirezd, Javier de la Matad, Barbara Klajnerta, Maria Bryszewskaa

Department of General Biophysics, University of Lodz, PolandLaboratory of Molecular Spectroscopy, Department of Chemistry, University of Lodz, PolandFaculty of Mathematics, Physics and Informatics, Comenius University, Bratislava, SlovakiaDepartamento Quimica Inorganica, Universidad de Alcala de Henares, Spain

r t i c l e i n f o

rticle history:eceived 14 July 2011eceived in revised form 25 January 2012ccepted 27 January 2012vailable online 14 February 2012

eywords:arbosilane dendrimersiposomes

a b s t r a c t

The aim of this work was to study interactions between cationic carbosilane dendrimers (CBS) and lipidbilayers or monolayers. Two kinds of second generation carbosilane dendrimers were used: NN16 withSi–O bonds and BDBR0011 with Si–C bonds. The results show that cationic carbosilane dendrimersinteract both with liposomes and lipid monolayers. Interactions were stronger for negatively chargedmembranes and high concentration of dendrimers. In liposomes interactions were studied by measuringfluorescence anisotropy changes of fluorescent labels incorporated into the bilayer. An increase in fluo-rescence anisotropy was observed for both fluorescent probes when dendrimers were added to lipids thatmeans the decreased membrane fluidity. Both the hydrophobic and hydrophilic parts of liposome bilayers

onolayernisotropyembrane fluidity

became more rigid. This may be due to dendrimers’ incorporation into liposome bilayer. For higher con-centrations of both dendrimers precipitation occurred in negatively charged liposomes. NN16 dendrimerinteracted stronger with hydrophilic part of bilayers whereas BDBR0011 greatly modified the hydropho-bic area. Monolayers method brought similar results. Both dendrimers influenced lipid monolayers andchanged surface pressure. For negatively charged lipids the monitored parameter changed stronger than

s. Mo

for uncharged DMPC lipid

. Introduction

Very often it is not a problem to create a drug but to transport itnto the cell. In the bloodstream drugs are exposed to many factorsike peptides or enzymes which can destroy them or interact withhem. For the drug to get into the right place in the body meanshat it has to pass membrane barrier and interact properly insidehe cell. Many publications are devoted to the problem of drug car-iers formation, synthesis and way of transport (Yokoyama, 2005;iaopeng et al., 2007; Sahoo et al., 2008; Chen et al., 2008; Bronich,010; Yuan et al., 2010). Drug carriers are substances that couldolve many problems in drug delivery. Those molecules should beble to improve the delivery and the effectiveness of drugs. More-ver, drug carriers are used to reduce cytotoxicity and improve drugetabolism (Petzinger and Geyer, 2006; Dong et al., 2010). They

re exerted in a controlled-release technology to prolong in vivorug actions (Jansen et al., 1994; Chen et al., 2008; Nanjwadeat al., 2009). Nowadays there are few systems of drug transport

∗ Corresponding author at: Department of General Biophysics, University of Lodz,41/143 Pomorska St., 90-236 Lodz, Poland. Tel.: +48 42 6354144;ax: +48 42 6354474.

E-mail address: domwro@biol.uni.lodz.pl (D. Wrobel).

009-3084/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.chemphyslip.2012.01.008

reover, NN16 dendrimer interacted stronger than the BDBR0011.© 2012 Elsevier Ireland Ltd. All rights reserved.

like liposomes, albumin microspheres, bioconjugates, virosomesor dendrimers (Bhardwaj and Burgess, 2010; Anada et al., 2009;Thakkar et al., 2005; Lua et al., 2002; Daemen et al., 2005; Najlah andD’Emanuele, 2006). Dendrimers are quite a new class of globularpolymers and because of their properties they generate high inter-est. Among their possible biomedical applications are drug transferor serving as DNA carriers. It is possible either by encapsulation intheir interiors or by bonding to the surface groups.

For the efficient transport of a medicine a drug carrier has to passthrough the cell membrane. Cell membranes are complex struc-tures made of lipids and proteins. To understand how dendrimerscan cross this barrier, first it is necessary to understand interactionsbetween these molecules and lipid bilayers. Model membranes likeliposomes are excellent research models for experiments becauseof their simple composition, easy preparation and a good enoughtime stability. In the literature there are numerous studies on inter-actions between mostly polyamido amine (PAMAM) dendrimersand liposomes (Ottaviani et al., 1998,1999; Castile et al., 1999;Purohit et al., 2001; Hong et al., 2004, 2006; Mecke et al., 2004,2005a,b; Klajnert and Epand, 2005; Lee and Larson, 2006; Klajnert

et al., 2006; Gardikis et al., 2006; Yan and Yu, 2009; Kelly et al., 2008,2009; Ionov et al., 2010; Smith et al., 2010; Wrobel et al., 2011;Tiriveedhi et al., 2011; Ionov et al., 2011). Dendrimers can eitherpass through the lipid bilayer or dendrimers-lipids micelles are

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02 D. Wrobel et al. / Chemistry and

reated (Lee and Larson, 2008). Some dendrimers can interact withipids by hydrophobic interactions between lipid acyl chains andhe hydrophobic dendrimers interior (Smith et al., 2010; Kelly et al.,009). It was shown that the strength of interaction depends mainlyn a size and charge of the molecule (Ottaviani et al., 1998,1999;iriveedhi et al., 2011) and the phase of lipids (Wrobel et al., 2011).

One class of those globular polymers are carbosilane dendrimersCBS). They were synthesized for siRNA and oligonucleotideelivery system. Bonding between dendrimers and siRNA orligonucleotide is based on electrostatic interactions. Dendrimersossess positively charged functional groups which could interactith negatively charged nucleotides backbone. In this work two

inds of dendrimers called BDBR0011 and NN16 were used. Firstf them possesses branches made of carbon–silicon bonds whichre water-stable (Fig. 1A). The other one is made of oxygen–silicononds and in aqueous solutions is slowly hydrolyzed (Fig. 1B).his property allows for gradually letting go cargos from den-rimers. In the literature it is said that degradation takes between

h and 24 h (Bermejo et al., 2007). The most important prop-rty of carbosilane dendrimers as a nucleic acids carrier is makingtable complexes with nucleic acid. This plays the main role inNA/RNA administration into the bloodstream because of pro-

ective property from sequestration and degradation by proteinsChonco et al., 2007; Shcharbin et al., 2007). Second generation ofhis dendrimer shows good toxicity profiles up to a concentrationf 5 �M (Ortega et al., 2007). Moreover, antibacterial properties ofhese dendrimers have been demonstrated and the most efficientre dendrimers of first and second generations. The antibacte-ial activity is related to the type of bacteria and dendrimerseneration (Rasines et al., 2009). In our studies we checked thenfluence of two cationic carbosilane dendrimers on bilayer flu-dity and surface pressure of lipid monolayers. NMR method wassed for stable BDBR0011 dendrimer to observe the type of inter-ction. We were working with uncharged pure DMPC lipid and twonionic lipids. Carbosilane dendrimers used in the study possess 16ationic functional groups. The molecular formula and moleculareights of those compounds are: NN16–C128H316 I16N16O8Si13

+16,w = 4 603.56 g/mol and BDBR0011–C144H348I16N16Si13

+16 Mw = 499.99 g/mol.

. Materials and methods

.1. Materials

Lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholineDMPC); dipalmitoylphosphatidylglicerol (DPPG); fluorescentrobes: 1,6-diphenyl-1,3,5-hexatriene (DPH); N,N,N-trimethyl--(6-phenyl-1,3,5-hexatriene-1-yl) phenylammonium-toluenesulfonate (TMA-DPH); Hepes buffer were purchasedrom Sigma Chemical Company. The 10 mM Hepes buffer pH 7.4as made in distilled water. Water-soluble carbosilane dendrimersere synthesized in the Departamento de Quimica Inorganica,niversidad de Alcala, Spain (Ortega et al., 2007; Bermejo et al.,007).

.2. Liposomes preparation

Phospholipids and fluorescent probes were dissolved in organicolvents. Appropriate amounts of lipid and probe solutions werelaced in a flask under vacuum conditions to evaporate the solvent.he resulting lipid film was hydrated with an appropriate volume

f 10 mM Hepes buffer at pH 7.4. Lipid/probe mixture was incu-ated above the lipid phase-transition temperature. Subsequentlyhe suspension was forced to pass >15 times through a polycarbon-te membrane of 100 nm porosity (Nuclepore, T-E), mounted in a

s of Lipids 165 (2012) 401– 407

mini-extruder (Avanti Polar Lipids) fitted with two 1000-�l Hamil-ton gastight syringes. The final lipid concentration was 500 �M, andthe phospholipid/fluorescent probe molar ratio was 500:1 (Ionovet al., 2009).

2.3. Characterization of liposomes

To characterize liposomes Zetasizer Nano-ZS, 635-nm lasermodule with detector at 173◦ (Malvern Instruments Ltd., Malvern,Worcestershire, UK) was used. The size of the particle was esti-mated by measuring Brownian motions and relating it to the sizeof the particles, whereas the zeta potential was calculated fromHenry equation using the data obtained by electrophoresis of thesample and measuring velocity of the particles by Laser DopplerVelocimetry (LDV). The 50 �M lipid suspension in 10 mM Hepesbuffer pH 7.4 was investigated at temperature 37 ◦C.

2.4. Steady-state fluorescence spectroscopy

Steady-state fluorescence anisotropy measurements were car-ried out with a LS-50B (Perkin-Elmer, U.K.) spectrofluorimeter. Tomonitor membrane fluidity of a bilayer, two fluorescent probeswere used. One of them - DPH, an apolar molecule, was incorpo-rated into the hydrophobic region of the liposome bilayer whileTMA-DPH was anchored near the region of lipid head groupsbecause of its positively charged amino groups which are locatedat the lipid/water interface. The phospholipid/fluorescent probemolar ratio was 500:1. The excitation and emission wavelengthswere 348 nm and 426 nm, respectively (Shinitzky and Barenholz,1974, 1978; Hirsch-Lerner et al., 1998; Tanfani et al., 1989). Theslit width of the excitation monochromator was 8 nm and the slitwidth of the emission monochromator was 6 nm for both labels.The cuvette holder was temperature controlled and the experimentwas carried out at 37 ◦C above the main transition of lipids. All den-drimers were dissolved in 10 mM Hepes buffer pH 7.4, and addedto the sample to reach the appropriate concentration.

The steady-state fluorescence polarization values (r) werecalculated by the fluorescence data manager programme usingJablonski’s equation:

r = (IVV − GIVH)(IVV + 2GIVH)

where IVV and IVH are the vertical and horizontal fluorescence inten-sities, respectively, to the vertical polarization of the excitation lightbeam. The factor G = IHV/IHH (grating correction factor) corrects thepolarizing effects of the monochromator.

2.5. Monolayers method

Experiments were performed using an instrument forLangmuir–Blodgett method. To scale down the method smallteflon cuvette was used with minimum volume of 4.5 ml. Sampleswere prepared by adding appropriate amounts of lipids on thesurface of Hepes buffer to achieve surface pressure of about31 mN/m which was a bit higher than required for the experiment.To solve the lipids pure chloroform was used for DMPC and themixture of DMPC + 30% DPPG whereas DPPG was dissolved ina chloroform/methanol mixture (3/1) (v/v). The concentrationof lipids was 3 mg/ml. To measure a surface pressure a paperplate (10 mm × 24 mm)–Wilhelmy plate was used (Tzung-Hanet al., 2008). When the stability of monolayer was achieved andthe surface pressure was about 28 mN/m (this value was treated

as a 0% saturation) dendrimers were added to the cuvette by aHamilton syringe through the special channel. The addition ofdendrimers was divided into three portions to get dendrimersconcentration of 0.5 �M, 1 �M and 3 �M in the cuvette. At the end

D. Wrobel et al. / Chemistry and Physics of Lipids 165 (2012) 401– 407 403

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Fig. 1. Structure of cationic carbosilan

f the measurement lipids were put on the surface to achieve theaturation (treated as a 100% saturation).

.6. NMR method

NMR spectra were recorded on Bruker Avance III 600 MHz for 1Hpectrometer equipped in standard NMR BBO probe. Samples wererepared in 10 mM Hepes buffer pH 7.4 in D2O. All spectra wereecorded at 25 ◦C with temperature stabilization and water sup-ression using presaturation. Spectra were calibrated on “rest” HDOignal at 4.74 ppm. 1H–1H NOESY spectra were recorded withoutradients using standard mixing time of 300 ms,

.7. Statistical analysis

Statistical analysis and exponential curve fitting were per-ormed using Statistica 9 (StatSoft) software. Results are expresseds mean ± standard error of the mean (S.E.M.).

. Results

.1. Characterization of the liposomes

Liposomes were prepared by extrusion method. By this methodmall unilamellar vesicles (SUV) are formed. All parameters whichharacterize neutral DMPC and negatively charged DPPG liposomesre placed into the Table 1.

.2. Steady-state fluorescent anisotropy measurements

Three kinds of lipids mixtures were used: pure dimyris-

oylphosphatidylcholine (DMPC), mixture of DMPC and 30% ofipalmitoylphosphatidylglycerol (DPPG) and pure DPPG. DMPC

iposomes do not bear any charge whereas liposomes composedf DMPC/30%DPPG mixture or pure DPPG possess negative charge

able 1haracteristics of liposomes.

Liposome Diameter (nm) Zeta potential (mV)

DMPC 143.8 ± 5.5 −2.4 ± 4.1DMPC + 30%DPPG 102.5 ± 6.8 −17.6 ± 2.7DPPG 101.2 ± 6.8 −18.1 ± 2.7

eneration 2 with Si–O or Si–C bonds.

on their surface. The changes in the fluorescence anisotropy showthat dendrimers interact with the liposomal membranes. Whenthis parameter increases it means that lipid bilayer becomes morerigid, reflecting the fact that dendrimers had probably moved intothe liposome bilayer. In the experiments two fluorescent probesDPH and TMA-DPH were used to monitor changes in hydrophobicregion and hydrophilic/hydrophobic interphase parts of the bilayer.Increase in anisotropy for DMPC liposomes was observed for bothfluorescent probes (Fig. 2).

Statistically significant changes in DPH and TMA-DPH fluo-rescence anisotropy were observed for DMPC liposomes, whichindicates that both investigated dendrimers affect the lipid orderpacking of DMPC membranes in hydrophilic and hydrophobicregions of the bilayer.

The addition of increasing concentrations of dendrimers leads toa change of probe fluorescence anisotropy, showing alterations inmembrane fluidity. The similar results were observed for mixture ofDMPC with 30% DPPG (Fig. 3) and for pure DPPG (Fig. 4) liposomes.

Both dendrimers are of similar size and possess 16 cationicgroups on their surface. For BDBR0011 dendrimers stronger inter-actions with liposomes labeled with DPH probe were observedwhereas with TMA-DPH labeled bilayers BDBR0011 interactedweaker than NN16. BDBR0011 caused changes in the fluidity inthe hydrophobic part of the bilayer and interacted weaker withlipids head groups. NN16 dendrimer interacted stronger with thehydrophilic part of a bilayer than with the hydrophobic one. Bothdendrimers interacted stronger with charged liposomes and thecontent of anionic lipids in the mixture was important.

3.3. Monolayer

As in the first method the same three kinds of lipids mix-tures were used: pure DMPC, mixture of DMPC and 30%DPPG andpure DPPG. The surface pressure of 28 mN/m was obtained whena monolayer in an ordered liquid-condensed phase was created.Membrane structure in this phase is comparable to the structureof a cell membrane. Moreover, the addition of anionic lipids simu-

lates charge like in a natural cell membrane. Interactions betweendendrimers and lipids monolayers are characterized by changes inthe surface pressure. When molecules interact with membrane anincrease of a surface pressure should be observed.

404 D. Wrobel et al. / Chemistry and Physics of Lipids 165 (2012) 401– 407

Fig. 2. Fluorescence anisotropy of (A) DPH rc-DPH = 0.075 ± 0.003 and (B) TMA-DPH rc-TMA-DPH = 0.170 ± 0.001 probes in DMPC liposome/dendrimer mixtures; �, dendrimerNN16, ©, dendrimer BDBR0011. rn , sample fluorescence anisotropy value, rc , control fluorescence anisotropy value in the absence of dendrimers. All data were expressed asmean ± S.E.M. n = 3; p < 0.05 for “*” point vs control.

F rc-TMA

d alue, re

cfmw

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ig. 3. Fluorescence anisotropy of (A) DPH rc-DPH = 0.094 ± 0.002 and (B) TMA-DPHendrimer NN16, ©, dendrimer BDBR0011. rn , sample fluorescence anisotropy vxpressed as mean ± S.E.M. n = 3; p < 0.01 for “*” point vs control.

Changes in surface pressure were observed for all studied

onfigurations. Both carbosilane dendrimers affected the sur-ace pressure of monolayers but NN16 dendrimer induced much

ore fluctuations than BDBR0011 (Fig. 5). In all samples treatedith NN16 the surface pressure increased two times more than

ig. 4. Fluorescence anisotropy of (A) DPH rc-DPH = 0.116 ± 0.001 and (B) TMA-DPH rc-TM

N16, ©, dendrimer BDBR0011. rn , sample fluorescence anisotropy value, rc , control fluean ± S.E.M. n = 3; p < 0.01 for “*” point vs control.

-DPH = 0.182 ± 0.001 probes in DMPC + 30%DPPG liposome/dendrimer mixtures; �,c , control fluorescence anisotropy value in absence of dendrimers. All data were

for BDBR0011. Dendrimers interacted stronger with negatively

charged monolayers than with uncharged ones. Measurementshave been performed for 3 concentrations of dendrimers 0.5 �M,1 �M and 3 �M but surface pressure changed only for the first con-centration, so was not concentration-dependent.

A-DPH = 0.212 ± 0.005 probes in DPPG liposome/dendrimer mixtures; �, dendrimerorescence anisotropy value in absence of dendrimers. All data were expressed as

D. Wrobel et al. / Chemistry and Physics of Lipids 165 (2012) 401– 407 405

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ig. 5. Surface pressure changes for A - BDBN0011 dendrimer; B - NN16 dendrimontrol.

.4. NMR measurements

By 1H–1H NOESY NMR spectra one can observe intermolecu-ar interactions between liposome and dendrimer. To determine

hich signal corresponds to this interaction the NMR spectra forach “separated” element like dendrimer, liposome and bufferere performed. In Fig. 6A 1H–1H interactions observed in theendrimers are shown. In Fig. 6B the additional signals from inter-ctions between the liposome and dendrimer (marked in circle andquare) can be seen.

. Discussion

As it was mentioned in Section 1, many reports are devotedo the topic of interactions between dendrimers and biologi-al membranes. The most explored dendrimers are PAMAM andolypropyleneimine (PPI) ones. In the literature a lot of evidencean be found that dendrimers either create holes in a bilayer (Mecket al., 2004, 2005a,b; Hong et al., 2004, 2006; Shcharbin et al., 2006;ee and Larson, 2006, 2008; Yan and Yu, 2009) or can be incorpo-ated into lipid structure (Klajnert et al., 2006; Kelly et al., 2008;

robel et al., 2011; Ionov et al., 2011). The strength of action isependent on charge and size of the molecule. The highest genera-ion dendrimers caused the greatest disturbances in a lipid bilayer

nd positively charged dendrimers more effectively interacted withiposomes (Ottaviani et al., 1998, 1999; Purohit et al., 2001; Klajnertt al., 2006; Tiriveedhi et al., 2011; Wrobel et al., 2011). How-ver, there is only one journal communication about carbosilane

Fig. 6. 1H–1H NOESY spectra of pure dendrimer BDBR0011

l data were expressed as mean ± S.E.M. n = 4; p < 0.01 “**”, p < 0.05 for “*” point vs

dendrimers and their interactions with model or cell membranes(Ionov et al., 2011).

The increase in fluorescence anisotropy was seen for all lipo-somes and fluorescent probes after CBS dendrimers addition. Thisindicates that dendrimers made lipid membranes more rigid.Changes in steady-state anisotropy observed for TMA-DPH probecould be explained by dendrimer interaction with anionic lipidhead groups and formation of ordered regions – dendrimers/lipidsdomains (Hirsch-Lerner et al., 1998). However, it must be stressedthat the steady-state measurements with continuous excitationand emission give only an average value of anisotropy which con-tains both dynamic and static effects. The separation of dynamicinformation from the effects due to constraints on the range oflipid motion is possible only by measuring the time-dependentanisotropy r(t). Two carbosilane dendrimers of second generationwere used – NN16 with Si–O bonds and BDBR0011 with Si–C bonds.It is surprising that they affected various regions of a bilayer andthe strength of interaction was different for each of them. Den-drimer with Si–O bonds interacted stronger with hydrophilic partof a bilayer whereas for denrimer with Si–C bonds more signifi-cant changes in fluidity were observed in the hydrophobic part oflipid membranes. The strength of interaction was related to thelipid composition and it was increasing when the concentration oflipids with the negative charge increased.

Similar results were obtained for the monolayer method.

Interactions of different strength were observed for both den-drimers and this depended also on lipid composition of avehicle. NN16 caused two times stronger changes in a surface

(A) and liposome/dendrimer BDBR0011 mixture (B).

4 Physic

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06 D. Wrobel et al. / Chemistry and

ressure than BDBR0011. Both dendrimers interacted strongerith negatively charged monolayers. The results suggest that

ationic carbosilane dendrimers can penetrate lipid monolay-rs or create ordered domains at the surface of lipid layer thateflects the fluidity changes observed in steady-state fluores-ence spectroscopy measurements. Observed disturbances wereoncentration and anionic-lipid-content-dependent. The only dif-erence between used dendrimers was the existence of eitheri–O bonds (NN16) or Si–C (BDBR0011) in the dendrimers.i–O bonds are not stable in water solutions where they areydrolyzed.

The NMR experiment results suggest that BDBR0011 dendrimeran penetrate lipid membranes and interact with acyl chains ofipids. Our suggestion is based on fact that proton signal about.4 ppm can only originate from tail ends in lipids. The typi-al region for proton resonances originating from headgroups isetween 3 ppm and 4 ppm, but we did not observe any interactionsetween dendrimers and lipids in this region. As the interactionsetween lipid heads and dendrimers were not observed by NMRethod, the fluidity changes in hydrophilic area could be connectedith mechanical interactions between lipid head groups duringendrimers penetration into lipid bilayer. We observed weak inter-ctions between terminal proton groups from tail end (–CH3 group)nd dendrimers. This interaction is much weaker than interactionsetween dendrimers and the rest of tail and it can suggest thatendrimers deeply penetrate the lipids.

Similar observations have been made for PAMAM dendrimers5 and G7 (Smith et al., 2010). In this article strong interac-

ions between dendrimers and acyl chains were explained by theydrophobic interior of a dendrimer molecule. There is not much

nformation about chemical properties of carbosilane dendrimersut the results can suggest the hydrophobicity of the dendrimer

nterior. There are no NMR data for NN16 dendrimer because ofnstability of this molecule.

Many reports have been published about mechanism of inter-ction between PAMAM dendrimers and liposomes. The resultsuggested that poly(amidoamine) dendrimers could interact withipid membranes even though they are quite rigid structures. Atow concentrations dendrimers can traverse the bilayer whereas atigher concentrations dendrimers-lipid micelles are created andhe structure of membrane is attenuated (Ottaviani et al., 1999;ee and Larson, 2008).

The mechanism of interaction between amphipathic den-rimers and lipid bilayer is connected with hydrophobic interactionPurohit et al., 2001; Klajnert et al., 2006; Wrobel et al., 2011).ome investigations show that dendrimers can create holes in lipidehicles (Mecke et al., 2004; Lee and Larson, 2008; Yan and Yu,009; Kelly et al., 2009). Tiriveedhi et al. (2011) concluded that

ow generation PAMAM dendrimers can bind electrostatically tohe lipid membrane but in fact, they were working with nega-ively charged liposomes. They observed aggregation of negativelyharged liposomes and dendrimers. The most important parame-ers which decided about investigated interaction are physical statef membrane and membrane surface pressure (Tiriveedhi et al.,011; Wrobel et al., 2011).

Carbosilane dendrimers are positively charged similarly toAMAM dendrimers so the mechanism of interaction with lipidembrane could be similar. The most probable mechanism of

arbosilane dendrimers and model membranes interaction is elec-rostatic binding. Carbosilane dendrimers posses 16 cationic aminoroups on their surface whereas DPPG is a negatively chargedipid. At the concentration above 20 �M in the sample precipitation

ccurred like for PAMAM and phosphorus-containing dendrimers.nteractions were observed for neutral DMPC liposomes. This coulde due to hydrophobic interactions as for PAMAM or phosphorus-ontaining dendrimers but there is no evidence that the interior

s of Lipids 165 (2012) 401– 407

of carbosilane dendrimer is hydrophobic (Tiriveedhi et al., 2011;Wrobel et al., 2011; Ionov et al., 2011).

5. Conclusions

In summary, carbosilane dendrimers interact with bothhydrophobic and hydrophilic part of bilayer. The mechanismof interaction is mainly based on electrostatic binding betweenmolecules and lipid vesicles. The interaction with nonchargedliposomes can be related to hydrophobic interactions betweendendrimers and lipids chain. These data provide the basis for thepotential use of carbosilane dendrimers as nucleic acids carriers.

Acknowledgements

Research was supported by the project “Biological Prop-erties and Biomedical Applications of Dendrimers” operatedwithin Foundation for Polish Science TEAM programme co-financed by the European Regional Development Fund, ProjectTEAM number TEAM/2008-1/5 and Polish-Slovak CooperationProject “Dendrimers as carriers for siRNA targeted against HIV-1virus–interactions with membranes”.

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