Articles

A Novel Drug Carrier: Lipophilic Drug-Loaded Polyglutamate/Polyelectrolyte Nanocontainers

Xin Rong Teng,*,†,‡ Dmitry G. Shchukin,*,† and Helmuth Mo¨hwald†

Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany, and School of MaterialsScience and Engineering, Tongji UniVersity, 200092, Shanghai, China

ReceiVed August 2, 2007. In Final Form: October 10, 2007

A novel lipophilic drug carrier, “oil-in-water” multifunctional composite nanocontainers, is developed by combiningultrasonic technique and layer-by-layer assembly. Polyglutamate/polyethyleneimine/poly(acrylic acid) nanocontainersloaded with the lipophilic drug, rifampicin, dissolved in soybean oil were fabricated. Raman confocal microscopy andscanning electron microscopy proved the successful incorporation of rifampicin into composite water-dispersiblepolyglutamate/polyelectrolyte nanocontainers. Transmission electron microscopy and confocal laser scanning microscopyindicated that the drug can be released by changing the pH value of the media due to the pH-responsive propertiesof the polyglutamate/polyelectrolyte shell.

Introduction

Many studies of pharmaceutical delivery systems have beencarried out to develop drug carriers that are suitable for deliveringa drug to the injured site. Among them, more attention has beenpaid to polymeric micelles,1 lipid nanocapsules,2-3 liposomes,or lipid microspheres.4-6 Emulsion delivery systems have beenwidely used to encapsulate drugs. Unfortunately, the solubilityof the shell material (i.e., polymers and lipids) in both organicsolvent and water is frequently required, high quantities ofsurfactants and co-surfactants like butanol increasing a potentialtoxicity. Lipid microspheres (LM), usually including soybeanoil and lecithin, are widely used in clinical medicine for parenteralnutrition. They are very stable and have no adverse effects. Drugscan be incorporated either into lipid microspheres, if they aresoluble in vegetable oil, or retained within the single lipidmembrane. Because of the avoidance of any harmful organicsolvent or toxic products, the lipid microspheres formed bydispersion of the LM particles in aqueous solution appear to besafe and efficient drug carriers.5 However, preparation of lipidmicrospheres usually needs a special high-pressure setup toemulsify oil solutions, which increases processing costs. To avoidharmful byproducts and, simultaneously, to explore some newfunctionalities of the potential drug carrier, we developed a simplemethod to fabricate a novel drug carrier system by combiningultrasonic technique and layer-by-layer (LbL) assembly protocol.This new method is the continuation of our previous work, whichdescribes the formation of water-dispersed polyglutamate/

polyelectrolyte nanocontainers filled with toluene/water-insolubledye.7 Herein, we use a lipophilic drug (rifampicin) and vegetableoil to fabricate a new type of bio-friendly drug carrier. Rifampicinis a semisynthetic antibiotic, which is derived from a form ofrifamycin that interferes with the synthesis of RNA and is usedto treat bacterial and viral diseases. It is widely used togetherwith isoniazid and streptomycin for the chemotherapy oftuberculosis.8

The core of the presented drug carrier contains the lipophilicdrug and vegetable oil as well as lecithin as an emulsifier, whichis similar to that for lipid microspheres. The shell of the containersis made of polyglutamate/polyethyleneimine (PEI)/poly(acrylicacid) (PAA) multilayers. The hydrophobic drug can be releasedby switching the polyglutamate/polyelectrolyte shell permeabilitythrough variation of environmental conditions, such as pHvalue9,10and ionic strength.11 Figure 1 shows the scheme of theformation of composite containers and the release of drugs bychanging the pH value. The polyelectrolyte shell can also bemodified to have some additional functionality. For example, ifthe containers are coated with appropriate antigens, they can betargeted to specific regions in the body.

Despite the high cost, lipid microspheres have already provedto be a safe carrier for drug targeting and have been put into themarket, such as lipo-prostaglandin E1, Lipo-steroid.5 However,composite drug carriers based on layer-by-layer depositiontechnology have not been reported yet. Fluorescein particleswere used as a model system for permeability studies of LbLassembled multilayers.12 Poly(styrenesulfonate) (PSS)/poly-(allylamine) (PAH) multilayers formed a polyelectrolyte shellon the fluorescein core. It was found that increased layer numbers

* Corresponding authors. E-mail: Dmitry.Shchukin@mpikg.mpg.de;sheila.teng@263.net.

† Max Planck Institute of Colloids and Interfaces.‡ Tongji University.(1) Jones, M. C.; Leroux, J. C.Eur. J. Pharm. Biopham.1999, 48, 101-111.(2) Malzert-Freon, A.; Vrignaud, S.; Saulnier, P.; Lisowski, V.; Benoıˆt, J P.;

Rault. S.Int. J. Pharm.2006, 320, 157-164.(3) Lamprecht, A.; Bouligand, Y.; Benoit, J.J. Controlled Release2002, 84,

59-68.(4) Yamaguchi, T.AdV. Drug DeliVery ReV. 1996, 20, 117-130.(5) Igarashi, R.; Takenaga, M.; Matsuda, T.AdV. Drug DeliVery ReV. 1996,

20, 147-154.(6) Mizushima, Y.AdV. Drug DeliVery ReV. 1996, 20, 113-115.

(7) Teng, X.; Shchukin, D. G.; Mo¨hwald, H.AdV. Funct. Mater.2007, 17,1273-1278.

(8) Kamat, B. P.; Seetharamappa, J.J. Chem. Sci.2005, 117, 649-655.(9) Antipov, A. A.; Sukhorukov, G. B.; Leporatti, S.; Radtchenko, I. L.; Donath,

E.; Mohwald, H.Colloids Surf. A2002, 198, 535-541.(10) Dejugnat, C.; Sukhorukov, G. B.Langmuir2004, 20, 7265-7269.(11) Ibarz, G.; Da¨hne, L.; Donath, E.; Mo¨hwald, H.AdV. Mater. 2001, 13,

1324-1327.(12) Antipov, A. A.; Sukhorukov, G. B.; Donath, E.; Mo¨hwald, H.J. Phys.

Chem. B2001, 105, 2281-2284.

383Langmuir2008,24, 383-389

10.1021/la702370k CCC: $40.75 © 2008 American Chemical SocietyPublished on Web 12/12/2007

decreased the shell permeability and resulted in prolonged dyedissolution. Besides, encapsulation of ibuprofen and furosemidemicrocrystals into the polyelectrolyte capsules with chitosan/dextran and PSS/gelatin shell, respectively, also resulted inprolonged release of the drugs at different pH values.13-14Manyanticancer drugs and photosensitive drugs are lipophilic ones15

and can be encapsulated into layer-by-layer assembled containers.They can be protected by the nanocontainer shell from chemical-,enzymatic-, and photodegradation to facilitate their deliveryefficiency. Lipophilic drugs are poorly absorbed after oraladministration; however, their absorption may be enhanced incombination with lipids. Although such a kind of containers haslargely been confined to lipophilic drugs, there are still plentifulopportunities for their application to modified hydrophilic drugs.For example, when drugs are not sufficiently lipophilic, derivationby alkyl esters could be achieved to obtain a hydrophobic analogue(e.g., hydrophobic mitomycin C derivatives).6,16

Experimental Section

Materials. Poly-L-glutamic acid sodium salt (polyglutamate,Mw

∼ 50000-100000), rifampicin, soybean oil, lecithin (soybeanphosphatidylcholine), polyethyleneimine (PEI,Mw ∼ 25000), poly-(acrylic acid) (PAA,Mw ∼ 50000) were purchased from Sigma-Aldrich (Germany). All compounds were used without any furtherpurification. PEI-Rhodamine B isothiocyanate was synthesized asdescribed elsewhere.17

Preparation of Drug-Loaded Polyglutamate/PolyelectrolyteNanocontainers and Release of Drug.The encapsulated drug,rifampicin, was first dissolved in soybean oil (5 wt % of rifampicinin soybean oil) and then the drug oil solution was placed over a 5%polyglutamate aqueous solution containing 1 mg/mL lecithin asemulsifier. A high-intensity ultrasonic horn was positioned at theaqueous-organic interface. The mixture was sonicated for 3 minin an ice bath employing an acoustic power of 150 W/cm2 at 20 kHzfrequency (Figure 1a). The unreacted oil solution was removed fromthe resulting drug-loaded emulsion by centrifugation and filteredthrough a membrane filter with 3µm diameter pore size (Millipore,Germany) several times. The polydispersity index of the resultingoil-loaded polyglutamate containers is 0.15. For fabrication of thelayer-by-layer assembled polyelectrolyte shell, we used the techniqueof subsequent addition of the polyelectrolyte solution (Figure 1b).18

PEI (0.05 mL) labeled with Rhodamine B or PAA solution (2 mg/mL in 0.5 M NaCl) was mixed with a 1 mLsuspension of drug-loaded polyglutamate containers at pH) 7. The mixture was gentlyshaken for 8 min. The next layers were deposited in the same manner.After eight alternating deposition steps, the final (PEI/PAA)4 layeredstructure was formed on top of the polyglutamate shell. Resultingpolyglutamate/(PEI/PAA)4 containers are stable for at least 4 monthsat 4 °C. Drug release was studied by incubating the containersuspension at pH) 1.4, pH) 11.4, and pH) 7.4, 37°C, 0.2 Mphosphate buffer solution (Figure 1c,d).

Characterization. Scanning electron microscopy (SEM) mea-surements were conducted using a Gemini Leo 1550 instrument.Samples were prepared by applying a drop of the suspension ontoglass wafer with sequential drying and gold sputtering. Transmissionelectron microscopy (TEM) (Zeiss EM 912 Omega) was used forthe visualization of the containers. Coated copper grids wereemployed to support the samples. Raman spectra were recorded bya confocal Raman microscope (CRM200, WITec) with diode-pumpedGreen laser excitation (532 nm) and a 100× oil (NA ) 1.25, Nikon)microscope objective. Confocal images were taken with a confocal

(13) Qiu, X.; Leporatti, S.; Donath, E.; Mo¨hwald, H. Langmuir 2001, 17,5375-5380.

(14) Ai, H.; Jones, S. A.; Villiers, M. M.; Lvov, Y. M.J. Controlled Release2003, 86, 59-68.

(15) Konan, Y. N.; Gurny, R.; Alle´mann, E.J. Photochem. Photobiol., B2002,66, 89-106.

(16) Sasaki, H.; Takakura, Y.; Hashida, M.; Kimura, T.; Sezaki, H.J.Pharmacodynam.1984, 7, 120-130.

(17) Kaschak, D. M.; Mallouk, T. E.J. Am. Chem. Soc.1996, 118, 4222-4223.

(18) Sukhorukov, G. B.; Donath, E.; Davis, S.; Lichtenfeld, H.; Caruso, F.;Popov, V. I.; Mohwald, H.Polym. AdV. Technol.1998, 9, 759-767.

Figure 1. Schematic illustration of the formation of the LbL-stabilized drug-loaded polyglutamate containers and drug release after pHchanges (PG, polyglutamate; PEI, polyethyleneimine; PAA, poly(acrylic acid); LbL, layer-by-layer). (a) Formation of oil-loaded polyglutamatecontainers in ultrasonic field; (b) layer-by-layer assembly of PEI/PAA shell; (c,d) swelling and dissolution of the container shell by changingthe pH value of the surrounding media.

384 Langmuir, Vol. 24, No. 2, 2008 Teng et al.

laser-scanning system TCLS attached to an inverse microscope fromLeica (Wetzlar, Germany) and equipped with a 100× oil immersionobjective having a numerical aperture of 1.4. Theú-potential of thecoated containers was measured by Zetasizer Nanoinstrument NanoZ equipment. Each value was averaged from three parallelmeasurements.

Results and Discussion

Formation and Stability of Drug-Loaded Polyglutamate/Polyelectrolyte Containers.A core-shell structure was formedwith rifampicin-loaded soybean oil inside and polyglutamateshell outside after ultrasonic treatment of the aqueous poly-glutamate/oil-rifampicin two-phase system. The mechanism ofcore-shell structure formation by ultrasonic treatment has beendiscussed in more detail previously.7,19-21 Addition of lecithinas an emulsifier can drastically increase the stability of containers.Figure 2 shows confocal laser scanning microscopy (CLSM)images of (PEI/PAA)4-coated oil-loaded (without drug) containerswith and without using lecithin as emulsifier. As compared withcontainers with lecithin, containers without lecithin were inclinedto aggregate after 3 weeks storage at 4°C and have larger size.The reason is that the lecithin has a negative charge and maystrongly interact with the polyglutamate shell, increasing thesurface charge of the polyglutamate shell, which results in betterelectrostatic repulsion between containers with lecithin/poly-glutamate shell.22 Another probable mechanism is that themiscibility between soybean oil and lecithin is critically importantfor the stability of the dispersed containers. Lecithin is knownto spontaneously form a bilayer at the oil/water interface.23

Soybean oil has limited solubility in lecithin bilayer membranes.It is often stabilized by the closely packed lecithin monolayer.When the lecithin content is under the solubility threshold insoybean oil, the lecithin monolayer does not completely coverthe hydrophobic surface of soybean oil droplets, which causesthe aggregation of the containers. However, when the contentof lecithin is high (in our work, 1 mg/mL lecithin content wasused), the lecithin monolayer covers the soybean oil completelyand stabilizes the dispersion. Thus, the obtained oil-lecithin containers can be stored at least for 2 months at 4°C, which is

especially important for long-term drug delivery system.Although lecithin-stabilized containers have sufficient surface

charge to produce better long-term stability, they cannot providecontrolled release of the encapsulated drug. To obtain this specificfunctionality of the containers, eight alternating monolayers (PEI/PAA) were deposited on the container surface via layer-by-layer

(19) Dibbern, E. M.; Toublan, F. J.; Suslick, K. S.J. Am. Chem. Soc.2006,128, 6540-6541.

(20) Suslick, K. S.; Grinstaff, K. J.; Kolbeck, K. J.; Wang, M.UltrasonicsSonochem.1994, 1, S56-S68.

(21) Avivi, S.; Gedanken, A.Biochem. J.2002, 366, 705-707.(22) Washington, C.AdV. Drug DeliVery ReV. 1996, 20, 131-145.(23) Asai, Y.J. Oleo Sci.2003, 52, 359-365.

Figure 2. CLSM images of soybean oil-loaded (without drug) polyglutamate/(PEI/PAA)4 containers without using lecithin as emulsifier:(a) Original containers in transmission mode; (b) containers after 3 weeks storage at 4°C in fluorescence mode.

Figure 3. ú-potential as a function of the layer number for containersduring PEI/PAA layer-by-layer deposition.

Figure 4. Structure of rifampicin.

Lipophilic Drug-Loaded Nanocontainers Langmuir, Vol. 24, No. 2, 2008385

assembly after formation of the oil-loaded polyglutamate shell.The emulsion became diluted after adding polyelectrolytes anda small quantity of flocculation was observed. When the firstPEI layer (2 mg/mL in 0.5 M NaCl) deposited on the uncoatedoil-lecithin surface, theú-potential of the containers changedfrom -32 to +33 mV (Figure 3). Following alternating PEI/PAA layer depositions results in surface recharging between-3and 21 mV, which indicates electrostatic assembly of polyelec-trolyte multilayers.

Encapsulation of Rifampicin into Polyglutamate/Polyelec-trolyte Containers.The lipophilic drug rifampicin (the structureis in Figure 4) was added to soybean oil to test the encapsulationprocedure. Lecithin (1 mg/mL solution) was used as an emulsifierdissolved in polyglutamate aqueous solution before mixing with

the oil phase. Raman confocal microscopy studies of the containerinterior (Figure 5) show a number of peaks corresponding to thepure soybean oil within the range 1100-1700, 2900 cm-1 forboth the empty and rifampicin-loaded containers, which indicatesthat soybean oil was successfully incorporated into the containers.For rifampicin-loaded containers, peaks at 1300 and 1380 cm-1

can be assigned to the vibrations ofυ (C-C) band and the vibrationof δ (CH3) band of rifampicin, respectively,24 which is notobserved for empty containers. Moreover, the small intensity ofthe broad band at 3200-3600 cm-1corresponding to the vibrationof the OH group of water is observed for all samples. This canbe interpreted as a signal from water entrapped in the poly-glutamate shell of containers. Hence, we can conclude that

Figure 5. Raman spectra of polyglutamate containers without polyelectrolyte multilayers: (a) Empty containers; (b) rifampicin-loadedcontainers.

Figure 6. SEM images of empty and rifampicin-loaded polyglutamate containers with and without polyelectrolyte multilayers: (a) Emptycontainers without polyelectrolyte layers; (b) rifampicin-loaded containers without polyelectrolyte layers; (c) empty containers with polyelectrolytelayers; (d) rifampicin-loaded containers with polyelectrolyte layers.

386 Langmuir, Vol. 24, No. 2, 2008 Teng et al.

rifampicin was successfully incorporated in the hydrophobicinterior of the containers, which have a hydrophilic polyglutamateshell.

SEM images show that containers without rifampicin areinclined to become clamp-shaped, especially when there are nopolyelectrolytes as additional protective layers (Figure 6a, suchas arrows indicate) and, in contrast, drug-loaded containers withor without additional polyelectrolyte shell keep their integrity(Figure 6b,d, arrows). This can be caused by drying duringpreparation of the SEM probes. The polyglutamate containershell is invaded by water molecules evaporating from the innercontainer, which results in rupture. The broken surface of oil-loaded containers tends to contract along the crack of thepolyglutamate shell, resulting in formation of clamp-shapedcontainers. When using polyelectrolytes as additional layers,containers mostly collapse instead of rupture and the amountof clamp-shaped containers decreases consequently (Figure6c, arrows). In a comparison of empty and drug-loadedcontainers, the latter ones keep their integrity, reducing the sizeto 200-600 nm due to the drug entrapped inside (Figure 6b,d,arrows).

Release of Rifampicin from Polyglutamate/PolyelectrolyteContainers.Multilayers of weak polyelectrolytes deposited ontothe container shell have semipermeable properties.9,10The innercharge of the polyelectrolyte shell depends on the pH value,which can be utilized for the pH-controlled release of encapsulated

material. To investigate the possibility of controlled rifampicinrelease, rifampicin-loaded containers with and without (PEI/PAA)4 multilayers were analyzed by TEM and CLSM aftertreatment at different pH values: pH) 1.4 (close to stomachpH) and pH ) 11.4. One hundred microliters of containersuspension was incubated in 200µL of HCl (pH 1.4) or NaOH(pH 11.4) for 16 h to demonstrate pH-controlled release.

For the containers without polyelectrolyte shells, drug releasewas observed only when incubating at pH 1.4 (Figure 7a). Figure7a shows more drug microcrystals (arrow) near a sphericalcontainer. This is because the hydrogen bonds or ion pairs betweentwo carboxylates ([RCO2-...M+...-O2CR] where M+ ) H+ orNa+) are destroyed in an acidic environment,19 which leadsto instability of the polyglutamate/lecithin composite. How-ever, it is interesting that intact polyglutamate/lecithincontainers were observed after treatment at pH 11.4 withoutevidence of rifampicin release (Figure 7b). This is probablybecause the added alkaline increases the ionization ratio ofpolyglutamate,provokingstronger intermolecularhydrogenbondsbetween two carboxylates and electrostatic interactions betweenpolyglutamate and lecithin, which keeps the stability of thecontainers and prevents the integrity of the shell and, as well,release of the encapsulated drug.

To investigate the influence of additional polyelectrolytemultilayers, the containers with polyelectrolyte shell weremonitored by CLSM after incubation for 16 h in both acid and

Figure 7. TEM images of polyglutamate containers without polyelectrolyte multilayers incubated at different pH for 16 h: (a) Containersincubated at pH 1.4; (b) containers incubated at pH 11.4.

Figure 8. Confocal images of polyglutamate/(PEI/PAA)4containers incubated at different pH conditions: (a) Original containers in transmissionmode; (b) containers incubated at pH 1.4 for 16 h in fluorescence mode; (c) containers incubated at pH 11.4 for 16 h in fluorescence mode.

Lipophilic Drug-Loaded Nanocontainers Langmuir, Vol. 24, No. 2, 2008387

alkaline conditions (Figure 8). CLSM images show that mostcontainers disappeared and only a few containers were observedafter treatment at pH 1.4 (Figure 8b). On the other hand, anincrease of the container size was found when incubating at pH11.4 (Figure 8c).

The kinetics of the rifampicin release is represented in Figure9. Both polyglutamate and polyglutamate/polyelectrolyte con-tainers release rifampicin quite rapidly at low pH (pH) 1.4) dueto the destruction of the polymer shell. However, the stabilizingeffect of the electrostatically adsorbed PEI/PAA shell is observedand the release time for polyglutamate/(PEI/PAA)4 containersis 3 times longer than that for pure polyglutamate ones. In contrast,the release of the rifampicin is not observed in alkaline pH forpure polyglutamate containers while deposition of the poly-electrolyte shell leads to the expansion of the polymer shellfollowed by formation of the pores permeable for rifampicin,demonstrating the release of the 25% of loaded drug within 16h.

Such behavior of containers with polyelectrolyte multilayerdecomposition at pH 1.4 and the size increase at pH 11.4 canbe interpreted as follows: At pH 1.4 most carboxylate groupsof the PAA are highly protonated and cannot compensate thecharge of PEI uncompensated ammonium groups. The electro-static repulsion between the positive charges results in a swellingof the whole structure. If the swelling pressure of the containerincreases, the remaining stabilizing electrostatic interactions aretoo weak to maintain the intact shell at such a low pH, resultingin container rupture due to Laplace’s law followed by dissolutionof the container shell and drug release. In contrast, in the caseof pH 11.4, PAA remains fully charged and PEI is deprotonated.25

Although the negative charges of PAA are repelled from eachother, resulting in swelling of containers, there are still someionic pairs of PEI and PAA due to the relatively weak basicenvironment; thus, the size of most containers increases, whichcould result in drug release from the pores of polyelectrolyteshell because the interior of polyglutamate/lecithin membranecould be defected by the swelling pressure. Similar results26

were reported for PAH/PMA polyelectrolyte capsules withaqueous interior, which were stable in the pH range from 2.5 to11.5.

Finally, rifampicin release from containers with and withoutpolyelectrolyte shell was investigated under physiological pHconditions in pH 7.4 (close to blood pH) phosphate buffer solutions(PBS) to simulate drug release in vivo. One milliliter of containersuspension was incubated in 5 mL of 0.2 M PBS, 37°C, withgentle stirring. After incubation, the containers were studied byTEM (Figure 10). Figure 10a shows that most containers withoutpolyelectrolyte layers were destroyed even in such a neutral pHenvironment, resulting in strong drug release after 21 days ofincubation. This effect could be caused by a synergetic effect ofboth H+ and phosphate on the stability of the polyglutamateshell, particularly on the possibility of hydrogen bond formation.However, with polyelectrolytes as protective layers, mostcontainers kept their integrity after incubation for 21 days inphosphate buffer (Figure 10b). Even after 40 days of incubation,there were still many intact containers (results not shown). Thus,the nanocontainers can maintain better integrity while poly-electrolytes are being used as protective layers, which helps toperform slow release of lipophilic drugs from the hydrophobiccontainer interior. Such protective properties of polyelectrolyteshell are important for controlled delivery and release, especiallyfor long-term drug delivery.

(24) Schrader, B.Raman Infrared Atlas of Organic Compounds, 2nd ed.;VCH: Weinheim, 1989.

(25) Lulevich, V. V.; Vinogradova. O. I.Langmuir 2004, 20, 2874-2878.(26) Mauser, T.; De´jugnat, C.; Sukhorukov, G. B.Macromol. Rapid Commun.

2004, 25, 1781-1785.

Figure 9. Release of the rifampicin from polyglutamate (1, 4) andpolyglutamate/(PEI/PAA)4 (2, 3) containers in acidic (pH) 1.4)and alkaline (pH) 11.4) media.

Figure 10. TEM images of polyglutamate containers with andwithout polyelectrolyte multilayers incubated at pH 7.4, PBS, 37°Cfor 21 days: (a) Containers without (PEI/PAA)4 shell incubated inPBS; (b) containers with (PEI/PAA)4 shell incubated in PBS.

388 Langmuir, Vol. 24, No. 2, 2008 Teng et al.

Conclusion

A novel drug carrier, “oil-in-water” multifunctional compositenanocontainers, were prepared by combined ultrasonic technologyand layer-by layer assembly protocol. A lipophilic drug,rifampicin, was successfully incorporated into composite water-dispersible polyglutamate/polyelectrolyte nanocontainers and itcan be released in different pH conditions due to the pH-responsiveproperties of the polyglutamate/polyelectrolyte shell. With useof rifampicin as a model, any other lipophilic drug can beencapsulated into the functional containers following thedescribedprocedure, which is especially important for long-term drugdelivery with controlled release. In addition, we can utilize suchcomposite nanocontainers as artificial cell membranes bychanging the lipid composition or use them to deliver genes

into target cells by regulating the charge on the polyelectrolytesurface as well as to target specific organs or tumor types byincorporating biochemical functions, e.g., proteins, receptors, orDNA sequences as monolayer constituent. This opens the wayfor creating shells with specific adhesion properties that are ofgreat potential for water-insoluble drug-delivery applications andfor diagnostics.

Acknowledgment. Dr. X. R. Teng thanks the China Scholar-ship Council for a research fellowship and we also thank RonaPitschke for electron microscopy analysis and Gabi Wienskolfor Raman microscopy measurement. This work was supportedby the BMBF project “NanoFuture”.

LA702370K

Lipophilic Drug-Loaded Nanocontainers Langmuir, Vol. 24, No. 2, 2008389