Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern), typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface). The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics.
References
[1]
Ehrlich, P. Collected Studies on Immunity; John Wiley & Sons: New York, NY, USA, 1906.
[2]
Kreuter, J. Nanoparticles—A historical perspective. Int. J. Pharm. 2007, 331, 1–10, doi:10.1016/j.ijpharm.2006.10.021.
[3]
Torchilin, V.P. Liposomes as delivery agents for medical imaging. Mol. Med. Today 1996, 2, 242–249, doi:10.1016/1357-4310(96)88805-8.
[4]
Lub-de Hooge, M.N.; Kosterink, J.G.; Perik, P.J.; Nijnuis, H.; Tran, L.; Bart, J.; Suurmeijer, A.J.; de Jong, S.; Jager, P.L.; de Vries, E.G. Preclinical characterisation of 111In-DTPA-trastuzumab. Br. J. Pharmacol. 2004, 143, 99–106, doi:10.1038/sj.bjp.0705915.
[5]
Van Den Bossche, B.; van Christophe, D.W. Receptor imaging in oncology by means of nuclear medicine: Current status. J. Clin. Oncol. 2004, 22, 3593–3607, doi:10.1200/JCO.2004.10.216.
[6]
Alyautdin, R.; Gothier, D.; Petrov, V.; Kharkevich, D.; Kreuter, J. Analgesic activity of the hexapeptide dalargin adsorbed on the surface of polysorbate 80-coated poly (butyl cyanoacrylate) nanoparticles. Eur. J. Pharm. Biopharm. 1995, 41, 44–48.
[7]
Kreuter, J.; Alyautdin, R.N.; Kharkevich, D.A.; Ivanov, A.A. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res. 1995, 674, 171–174, doi:10.1016/0006-8993(95)00023-J.
[8]
Kreuter, J.; Gelperina, S. Use of nanoparticles for cerebral cancer. Tumori 2008, 94, 271–277.
[9]
Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv. Drug. Deliv. Rev. 2001, 47, 65–81, doi:10.1016/S0169-409X(00)00122-8.
[10]
Kreuter, J. Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain. J. Nanosci. Nanotechnol. 2004, 4, 484–488, doi:10.1166/jnn.2003.077.
[11]
Senior, J.; Crawley, J.C.; Gregoriadis, G. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim. Biophys. Acta 1985, 839, 1–8, doi:10.1016/0304-4165(85)90174-6.
Müller, R.H. Colloidal Carriers for Controlled Drug Delivery and Targeting—Modification, Characterization and in vivo Distribution; CRC Press: Boca Raton, FL, USA, 1991.
[14]
Wilkins, D.J.; Myers, P.A. Studies on the relationship between the electrophoretic properties of colloids and their blood clearance and orrat, g.d.i.t. Br. J. Exp. Pathol. 1966, 47, 568–576.
[15]
Schwendener, R.A.; Lagocki, P.A.; Rahman, Y.E. The effects of charge and size on the interaction of unilamellar liposomes with macrophages. Biochim. Biophys. Acta 1984, 772, 93–101, doi:10.1016/0005-2736(84)90521-2.
[16]
Müller, R.H.; Davis, S.S.; Illum, L.; Mak, E. Particle charge and surface hydrophobicity of colloidal drug carriers. In Targeting of Drugs with Synthetic Systems; Gregoriadis, G., Senior, J., Poste, G., Eds.; Plenum Press: New York, NY, USA, 1986; pp. 239–263.
[17]
Müller, R.H.; Davis, S.S.; Illum, L.; Mak, E. Surface Characterisation of Colloidal Drug Carriers Coated with Polymers; ACS: Washington, WA, USA, 1986; pp. 161–162.
[18]
Mak, E. Determination of the Surface Hydrophobicity of Colloidal Drug Carriers using a Rose Bengal Binding Method. Acta Pharm. Technol. Int. J. Drug Formul. Biopharm. 1986, 32, 215–228.
[19]
Lukowski, G.; Müller, R.H.; Müller, B.W.; Dittgen, M. Acrylic acid copolymer nanoparticles for drug delivery. I: Characterization of the surface properties relevant for in vivo organ distribution. Int. J. Pharm. 1992, 84, 23–31, doi:10.1016/0378-5173(92)90211-J.
[20]
Krekeler, C.; Ziehr, H.; Klein, J. Physical methods for characterization of microbial surfaces. Experientia 1989, 45, 1047–1055, doi:10.1007/BF01950157.
[21]
Carstensen, H.; Müller, B.W.; Müller, R.H. Adsorption of ethoxylated surfactants on nanoparticles. I. Characterization by Hydrophobic Interaction Chromatography. Int. J. Pharm. 1991, 67, 29–37, doi:10.1016/0378-5173(91)90262-M.
[22]
Wallis, K.H.; Müller, R.H. Determination of the surface hydrophobicity of colloidal dispersions by mini-hydrophobic interaction chromatography. Pharm. Ind. 1999, 55, 1124–1128.
[23]
Illum, L.; Davis, S.S.; Müller, R.H.; Mak, E.; West, P. The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer-poloxamine 908. Life Sci. 1987, 40, 367–374, doi:10.1016/0024-3205(87)90138-X.
[24]
Müller, R.H.; Lück, M.; Harnisch, S.; Thode, K. Intravenously Injected Particles; Surface Properties and Interaction with Blood Proteins—The Key Determining the Organ Distribution. In Scientific and Clinical Applications of Magnetic Carriers; Schütt, W., Teller, J., H？feli, U., Zborowski, M., Eds.; Plenum Press: New York, NY, USA, 1997; pp. 135–148.
[25]
Illum, L.; Davis, S.S. Targeting of colloidal particles to the bone marrow. Life Sci. 1987, 40, 1553–1560, doi:10.1016/0024-3205(87)90120-2.
[26]
Juliano, R.L. Factors affecting the clearance kinetics and tissue distribution of liposomes, microspheres and emulsions. Adv. Drug Deliv. Rev. 1988, 2, 31–54, doi:10.1016/0169-409X(88)90004-X.
[27]
Müller, R.H.; Heinemann, S. Surface Modelling of Microparticles as Parenteral Systems with High Tissue Affinity. In Bioadhesion-Possibilities and Future Trends; Gurny, R., Junginger, H.E., Eds.; Wissenschaftliche Verlagsgesellschaft: Stuttgart, Germany, 1989; pp. 202–214.
[28]
Müller, R.H. Differential adsorption for the targeting of drug carriers. Acta Pharm. Technol. Int. J. Drug Formul. Biopharma. 1990, 36, 34.
[29]
Davis, S.S.; Illum, L.; Moghimi, S.M.; Davis, M.C.; Porter, C.J.H.; Muir, I.S.; Brindley, A.; Christy, N.M.; Norman, M.E.; Williams, P.; et al. Microspheres for targeting drugs to specific body sites. J. Contr. Release 1993, 24, 157–163, doi:10.1016/0168-3659(93)90175-5.
[30]
Armstrong, T.I.; Davies, M.C.; Illum, L. Human serum albumin as a probe for protein adsorption to nanoparticles: Relevance to biodistribution. J. Drug Target. 1997, 4, 389–398, doi:10.3109/10611869709017896.
[31]
Basinska, T. Adsorption studies of human serum albumin, human gamma-globulins, and human fibrinogen on the surface of p(S/PGL) microsphere. J. Biomater. Sci. Polym. Ed. 2001, 12, 1359–1371, doi:10.1163/156856202753419277.
[32]
Absolom, D.R.; Zingg, W.; Neumann, A.W. Protein adsorption to polymer particles: Role of surface properties. J. Biomed. Mat. Res. 1987, 21, 161–171, doi:10.1002/jbm.820210202.
[33]
Pieper, R.; Gatlin, C.L.; Makusky, A.J.; Russo, P.S.; Schatz, C.R.; Miller, S.S.; Su, Q.; McGrath, A.M.; Estock, M.A.; Parmar, P.P.; et al. The human serum proteome: display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins. Proteomics 2003, 3, 1345–1364, doi:10.1002/pmic.200300449.
[34]
Paulke, B.R.; M？glich, P.; Knippel, E.; Budde, A.; Nitzsche, R.; Müller, R.H. Electrophoretic 3D-mobility profiles of latex particles with different surface groups. Langmuir 1995, 11, 70–74, doi:10.1021/la00001a015.
[35]
Lück, M.; Paulke, B.R.; Schr？der, W.; Müller, R.H. Two-dimensional electrophoresis (2-DE) for the determination of plasma proteins adsorbed on model drug carriers. In Future Strategies for Drug Delivery with Particulate Systems; Diederichs, J.E., Müller, R.H., Eds.; CRC Press: Boca Raton, FL, USA, 1998; pp. 109–117.
[36]
Müller, R.H.; Rühl, D.; Lück, M.; Paulke, B.R. Influence of fluorescent labelling of polystyrene particles on phagocytic uptake, surface hydrophobicity, and plasma protein adsorption. Pharm. Res. 1997, 14, 18–24, doi:10.1023/A:1012043131081.
[37]
Lück, M.; Schr？der, W.; Harnisch, S.; Thode, K.; Blunk, T.; Paulke, B.R.; Kresse, M.; Müller, R.H. Identification of plasma proteins facilitated by enrichment on particulate surfaces: Analysis by two-dimensional electrophoresis and N-terminal microsequencing. Electrophoresis 1997, 18, 2961–2967, doi:10.1002/elps.1150181538.
[38]
Lück, M.; Paulke, B.R.; Schr？der, W.; Blunk, T.; Müller, R.H. Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics. J. Biomed. Mat. Res. 1998, 39, 478–485, doi:10.1002/(SICI)1097-4636(19980305)39:3<478::AID-JBM19>3.0.CO;2-6.
[39]
Lück, M.; Schr？der, W.; Paulke, B.R.; Blunk, T.; Müller, R.H. Complement activation by model drug carriers for intravenous application: Determination by two-dimensional electrophoresis. Biomaterials 1999, 20, 2063–2068, doi:10.1016/S0142-9612(99)00110-6.
[40]
Gessner, A.; Lieske, A.; Paulke, B.R.; Müller, R.H. Functional groups on polystyrene model nanoparticles: Influence on protein adsorption. J. Biomed. Mat. Res. 2003, 65, 319–326.
[41]
Gessner, A.; Paulke, B.R.; Müller, R.H.; G？ppert, T.M. Protein rejecting properties of PEG-grafted nanoparticles: Influence of PEG-chain length and surface density evaluated by two-dimensional electrophoresis and bicinchoninic acid (BCA)-proteinassay. Die Pharm. 2006, 61, 293–297.
[42]
Gessner, A.; Waicz, R.; Lieske, A.; Paulke, B.; M？der, K.; Müller, R.H. Nanoparticles with decreasing surface hydrophobicities: Influence on plasma protein adsorption. Int. J. Pharm. 2000, 196, 245–249, doi:10.1016/S0378-5173(99)00432-9.
[43]
Gessner, A.; Lieske, A.; Paulke, B.; Müller, R.H. Influence of surface charge density on protein adsorption on polymeric nanoparticles: Analysis by two-dimensional electrophoresis. Eur. J. Pharm. Biopharm. 2002, 54, 165–170, doi:10.1016/S0939-6411(02)00081-4.
[44]
Thode, K.; Lück, M.; Semmler, W.; Müller, R.H.; Kresse, M. Determination of plasma protein adsorption on magnetic iron oxides: Sample preparation. Pharm. Res. 1997, 14, 905–910, doi:10.1023/A:1012104017761.
[45]
Thode, K.; Lück, M.; Schr？der, W.; Blunk, T.; Müller, R.H.; Kresse, M. The influence of the sample preparation on plasma protein adsorption patterns on polysaccharide-stabilized iron oxide particles and N-terminal microsequencing of unknown proteins. J. Drug Target. 1998, 5, 459–469, doi:10.3109/10611869808997872.
[46]
Lind, K.; Kresse, M.; Müller, R.H. Comparison of protein adsorption patterns onto differently charged hydrophilic superparamagnetic iron oxide particles obtained in vitro and ex vivo. Electrophoresis 2001, 22, 3514–3521, doi:10.1002/1522-2683(200109)22:16<3514::AID-ELPS3514>3.0.CO;2-Q.
[47]
Lind, K.; Kresse, M.; Müller, R.H. Evaluation of desorption of proteins adsorbed to hydrophilic surfaces by two-dimensional electrophoresis. Proteomics 2001, 1, 1059–1066, doi:10.1002/1615-9861(200109)1:9<1059::AID-PROT1059>3.0.CO;2-V.
[48]
Petri, B.; Bootz, A.; Khalansky, A.; Hekmatara, T.; Müller, R.H.; Uhl, R.; Kreuter, J.; Gelperina, S. Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: Revisiting the role of surfactants. J. Contr. Release 2007, 117, 51–58, doi:10.1016/j.jconrel.2006.10.015.
[49]
Kreuter, J.; Petrov, V.E.; Kharkevich, D.A.; Alyautdin, R.N. Influence of the type of surfactant on the analgesic effects induced by the peptide dalargin after its delivery across the blood-brain barrier using surfactant-coated nanoparticles. J. Contr. Release 1997, 49, 81–87, doi:10.1016/S0168-3659(97)00061-8.
[50]
Kreuter, J.; Shamenkov, D.; Petrov, V.; Ramge, P.; Cychutek, K.; Koch-Brandt, C.; Alyautdin, R. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J. Drug Target. 2002, 10, 317–325, doi:10.1080/10611860290031877.
[51]
Steiniger, S.C.; Kreuter, J.; Khalansky, A.S.; ISkidan, N.; Bobruskin, A.I.; Smirnova, Z.S.; Severin, S.E.; Uhl, R.; Kock, M.; Geiger, K.D.; et al. Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int. J. Cancer 2004, 109, 759–767, doi:10.1002/ijc.20048.
[52]
Kreuter, J.; Ramge, P.; Petrov, V.; Hamm, S.; Gelperina, S.E.; Engelhardt, B.; Alyautdin, R.; von Briesen, H.; Begley, D.J. Direct evidence that polysorbate-80-coated poly (butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm. Res. 2003, 20, 409–416, doi:10.1023/A:1022604120952.
[53]
Gref, R.; Lück, M.; Quellec, P.; Marchand, M.; Dellacherie, E.; Harnisch, S.; Blunk, T.; Müller, R.H. "Stealth” corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf. B Biointerfaces 2000, 18, 301–313, doi:10.1016/S0927-7765(99)00156-3.
[54]
Rouzes, C.; Gref, R.; Leonard, M.; Delgado, A.D.; Dellacherie, E. Surface modification of poly(lactic acid) nanospheres using hydrophobically modified dextrans as stabilizers in an o/w emulsion/evaporation technique. J. Biomed. Mat. Res. 2000, 50, 557–565, doi:10.1002/(SICI)1097-4636(20000615)50:4<557::AID-JBM11>3.0.CO;2-R.
[55]
Owens, D.E., III; Peppas, N.A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 2006, 307, 93–102, doi:10.1016/j.ijpharm.2005.10.010.
[56]
Meng, H.C.; Kuyama, T.; Thompson, S.W., II; Ferrell, J.F. Toxicity Testing of Fat Emulsions. I. Tolerance Study of Long-Term Intravenous Administration of Intralipid in Rats. Am. J. Clin. Nutr. 1965, 16, 29–36.
[57]
Hochstrasser, D.F.; Funk, M.; Appel, R.D.; Pun, T.; James, R.W.; Hochstrasser, A.C.; Scherrer, J.R.; Pellegrini, C.; Müller, A.F. From biopsy to automatic diagnosis. Schweiz. Med. Wochenschr. 1990, 120, 1862–1866.
Kim, H.R.; Andrieux, K.; Delomenie, C.; Chacun, H.; Appel, M.; Desmaele, D.; Taran, F.; Georgin, D.; Couvreur, P.; Taverna, M. Analysis of plasma protein adsorption onto PEGylated nanoparticles by complementary methods: 2-DE, CE and Protein Lab-on-chip system. Electrophoresis 2007, 28, 2252–2261.
[60]
Liu, G.; Men, P.; Harris, P.L.; Rolston, R.K.; Perry, G.; Smith, M.A. Nanoparticle iron chelators: A new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance. Neurosci. Lett. 2006, 406, 189–193, doi:10.1016/j.neulet.2006.07.020.
[61]
Dobrovolskaia, M.A.; Aggarwal, P.; Hall, J.B.; McNeil, S.E. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol. Pharmacol. 2008, 5, 487–495, doi:10.1021/mp800032f.
Leroux, J.C.; Gravel, P.; Balant, L.; Volet, B.; Anner, B.M.; Allemann, E.; Doelker, E.; Gurny, R. Internalization of poly(D,L-lactic acid) nanoparticles by isolated human leukocytes and analysis of plasma proteins adsorbed onto the particles. J. Biomed. Mat. Res. 1994, 28, 471–481, doi:10.1002/jbm.820280410.
[64]
Allemann, E.; Gravel, P.; Leroux, J.C.; Balant, L.; Gurny, R. Kinetics of blood component adsorption on poly(D,L-lactic acid) nanoparticles: Evidence of complement C3 component involvement. J. Biomed. Mat. Res. 1997, 37, 229–234, doi:10.1002/(SICI)1097-4636(199711)37:2<229::AID-JBM12>3.0.CO;2-9.
[65]
Price, M.E.; Cornelius, R.M.; Brash, J.L. Protein adsorption to polyethylene glycol modified liposomes from fibrinogen solution and from plasma. Biochim. Biophys. Acta 2001, 1512, 191–205, doi:10.1016/S0005-2736(01)00330-3.
[66]
Cornelius, R.M.; Archambault, J.G.; Berry, L.; Chan, A.K.; Brash, J.L. Adsorption of proteins from infant and adult plasma to biomaterial surfaces. J. Biomed. Mat. Res. 2002, 60, 622–632, doi:10.1002/jbm.10117.
[67]
Blunk, T.; Hochstrasser, D.F.; Sanchez, J.C.; Müller, B.W.; Müller, R.H. Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface-modified latex particles evaluated by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 1993, 14, 1382–1387, doi:10.1002/elps.11501401214.
[68]
Jahangir, R.; McCloskey, C.B.; Clung, W.G.M.; Labow, R.S.; Brash, J.L.; Santerre, J.P. The influence of protein adsorption and surface modifying macromolecules on the hydrolytic degradation of a poly(ether-urethane) by cholesterol esterase. Biomaterials 2003, 24, 121–130, doi:10.1016/S0142-9612(02)00269-7.
[69]
Archambault, J.G.; Brash, J.L. Protein resistant polyurethane surfaces by chemical grafting of PEO: Amino-terminated PEO as grafting reagent. Colloids Surf. B Biointerfaces 2004, 39, 9–16, doi:10.1016/j.colsurfb.2004.08.009.
[70]
Unsworth, L.D.; Sheardown, H.; Brash, J.L. Protein resistance of surfaces prepared by sorption of end-thiolated poly(ethylene glycol) to gold: Effect of surface chain density. Langmuir 2005, 21, 1036–1041, doi:10.1021/la047672d.
[71]
Leroux, J.-C.; Alleman, E.; de Jaeghere, F.; Doelker, E.; Gurny, R. Biodegradable nanoparticles: From sustained release formulations to improved site specific drug delivery. J. Contr. Release 1996, 39, 339–350, doi:10.1016/0168-3659(95)00164-6.
[72]
Dobrovolskaia, M.A.; Guszcysski, T.; Specht, S.; McLeland, C.B. NCL Method ITA-4—Analysis of Nanoparticle Interaction with Plasma Proteins by 2D PAGE. Available online: http://ncl.cancer.gov/NCL_Method_ITA-4.pdf (accessed on 22 May 2011).
[73]
G？ppert, T.M.; Müller, R.H. Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug targeting. Int. J. Pharm. 2005, 302, 172–186, doi:10.1016/j.ijpharm.2005.06.025.
[74]
G？ppert, T.M.; Müller, R.H. Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns. J. Drug Target. 2005, 13, 179–187, doi:10.1080/10611860500071292.
[75]
G？ppert, T.M.; Müller, R.H. Alternative sample preparation prior to two-dimensional electrophoresis protein analysis on solid lipid nanoparticles. Electrophoresis 2004, 25, 134–140, doi:10.1002/elps.200305690.
[76]
G？ppert, T.M.; Müller, R.H. Plasma protein adsorption of Tween 80- and poloxamer 188-stabilized solid lipid nanoparticles. J. Drug Target. 2003, 11, 225–231, doi:10.1080/10611860310001615956.
[77]
Müller, R.H.; Harnisch, S. Physico-chemical characterization of propofol-loaded emulsions and interaction with plasma proteins. Eur. J. Hosp. Pharm. 2000, 6, 24–31.
[78]
Harnisch, S.; Müller, R.H. Plasma protein adsorption patterns on emulsions for parenteral administration: Establishment of a protocol for two-dimensional polyacrylamide electrophoresis. Electrophoresis 1998, 19, 349–354, doi:10.1002/elps.1150190233.
[79]
Harnisch, S.; Müller, R.H. Adsorption kinetics of plasma proteins on oil-in-water emulsions for parenteral nutrition. Eur. J. Pharm. Biopharm. 2000, 49, 41–46, doi:10.1016/S0939-6411(99)00064-8.
[80]
Schmidt, S.; Müller, R.H. Plasma protein adsorption patterns on surfaces of Amphotericin B-containing fat emulsions. Int. J. Pharm. 2003, 254, 3–5, doi:10.1016/S0378-5173(02)00667-1.
[81]
Blunk, T. Plasmaproteinadsorption auf kolloidalen Arzneistofftr？gern. Ph.D. Thesis, Christian-Albrechts-Universit？t, Kiel, Germany, 1994.
[82]
Gessner, A.; Paulke, B.R.; Müller, R.H. Analysis of plasma protein adsorption onto polystyrene particles by two-dimensional electrophoresis: Comparison of sample application and isoelectric focusing techniques. Electrophoresis 2000, 21, 2438–2442, doi:10.1002/1522-2683(20000701)21:12<2438::AID-ELPS2438>3.0.CO;2-F.
[83]
Diederichs, J.E. Plasma protein adsorption patterns on liposomes: Establishment of analytical procedure. Electrophoresis 1996, 17, 607–611, doi:10.1002/elps.1150170332.
[84]
G？ppert, T.M. Plasma protein adsorption on parenterally administered colloidal drug carriers for crossing the blood brain barrier. Ph.D. Thesis, Freie Universit？t, Berlin, Germany, 2005.
[85]
Thode, K. Specific contrast agents for magnetic resonance tomography: Physico-chemical characterisation and studies on plasma protein adsorption. PhD Thesis, Freie Universit？t, Berlin, Germany, 1996.
[86]
Camner, P.; Lundborg, M.; Lastbom, L.; Gerde, P.; Gross, N.; Jarstrand, C. Experimental and calculated parameters on particle phagocytosis by alveolar macrophages. J. Appl. Physiol. 2002, 92, 2608–2616.
[87]
Moghimi, S.M.; Muir, I.S.; Illum, L.; Davis, S.S.; Kolb-Bachofen, V. Coating particles with a block co-polymer (poloxamine-908) suppresses opsonization but permits the activity of dysopsonins in the serum. Biochim. Biophys. Acta 1993, 1179, 157–165, doi:10.1016/0167-4889(93)90137-E.
[88]
Ogawara, K.; Furumoto, K.; Nagayama, S.; Minato, K.; Higaki, K.; Kai, T.; Kimura, T. Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: Implications for rational design of nanoparticles. J. Contr. Release 2004, 100, 451–455, doi:10.1016/j.jconrel.2004.07.028.
[89]
O’Mullane, J.E.; Artursson, P.; Tomlinson, E. Biopharmaceutics of microparticulate drug carriers. Ann. N. Y. Acad. Sci. 1987, 507, 120–140, doi:10.1111/j.1749-6632.1987.tb45796.x.
[90]
Liliemark, E.; Sjostrom, B.; Liliemark, J.; Peterson, C.; Kallberg, N.; Larsson, B.S. Targeting of teniposide to the mononuclear phagocytic system (MPS) by incorporation in liposomes and submicron lipid particles: An autoradiographic study in mice. Leuk. Lymphoma 1995, 18, 113–118, doi:10.3109/10428199509064930.
[91]
Blunk, T.; Lück, M.; Calv？r, A.; Hochstrasser, D.F.; Sanchez, J.C.; Müller, B.W.; Müller, R.H. Kinetics of Plasma Protein Adsorption on Model Particles for Controlled Drug Delivery and Drug Targeting. Eur. J. Pharma. Biopharm. 1996, 42, 262–268.
[92]
Vroman, L.; Adams, A.L.; Fischer, G.C.; Munoz, P.C. Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces. Blood 1980, 55, 156–159.
[93]
Vroman, L.; Adams, A.L. Adsorption of proteins out of plasma and solutions in narrow spaces. J. Colloid Interface Sci. 1986, 111, 391–402, doi:10.1016/0021-9797(86)90042-1.
[94]
Rabilloud, T. Solubilization of proteins for electrophoretic analyses. Electrophoresis 1996, 17, 813–829, doi:10.1002/elps.1150170503.
[95]
Rabilloud, T.; Adessi, C.; Giraudel, A.; Lunardi, J. Improvement of the solubilization of proteins in two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 1997, 18, 307–316, doi:10.1002/elps.1150180303.
[96]
Benita, S.; Levy, M.Y. Submicron emulsions as colloidal drug carriers for intravenous administration: Comprehensive physicochemical characterization. J. Pharm. Sci. 1993, 82, 1069–1079, doi:10.1002/jps.2600821102.
Wretlind, A. Development of fat emulsions. J. Parenter. Enter. Nutr. 1981, 5, 230–235.
[99]
Wretlind, A. Recollections of pioneers in nutrition: Landmarks in the development of parenteral nutrition. J. Am. Coll. Nutr. 1992, 11, 366–373.
[100]
Davis, S.S.; Illum, L.; Müller, R.H.; Landry, F.; Wright, J.; Harper, G. The effect of infused fat emulsions on reticuloendothelial function in the rabbit. Clin. Nutr. 1990, 9, 260–265, doi:10.1016/0261-5614(90)90034-P.
[101]
Davis, S.S.; Washington, C.; West, P.; Illum, L.; Liversidge, G.; Sternson, L.; Kirsh, B.R. Lipid emulsions as drug delivery systems. Ann. N. Y. Acad. Sci. 1987, 507, 75–88, doi:10.1111/j.1749-6632.1987.tb45793.x.
[102]
Davis, S.S.; Illum, L.; West, P.; Galloway, M. Studies on the fate of fat emulsions following intravenous administration to rabbits and the effect of added electrolyte. Clin. Nutr. 1987, 6, 13–19.
[103]
Harnisch, S.; Müller, R.H. Analysis of adsorbed plasma proteins on commercial emulsions for parenteral nutrition. In Proceedings of International Symposium on Controlled Release and Bioactive Materials, Stockholm, Sweden, 1997.
[104]
Hochstrasser, D.F.; Harrington, M.G.; Hochstrasser, A.C.; Miller, M.J.; Merril, C.R. Methods for increasing the resolution of two-dimensional protein electrophoresis. Anal. Biochem. 1988, 173, 424–435.
[105]
Schmidt, S. Parenteral o/w emulsions: Drug incorporation and interaction with plasma proteins. Ph.D. Thesis, Freie Universit？t Berlin, Berlin, Germany, 2002.
[106]
Gogos, C.A.; Kalfarentzos, F. Total parenteral nutrition and immune system activity: A review. Nutrition 1995, 11, 339–344.
[107]
Eckart, J.; Adolph, M.; van der Mühlen, U.; Naab, V. Fat emulsions containing medium chain triglycerides in parenteral nutrition of intensive care patients. J. Parenter. Enteral Nutr. 1980, 4, 360–366.
[108]
Hedeman, H.; Brondsted, H.; Mullertz, A.; Frokjaer, S. Fat emulsions based on structured lipids (1,3-specific triglycerides): An investigation of the in vivo fate. Pharm. Res. 1996, 13, 725–728, doi:10.1023/A:1016095415849.
[109]
Harnisch, S.; Blunk, T.; Müller, R.H. The Kinetics of Plasma Protein Adsorption on Oil-in-Water Emulsions. In Proceedings of Electrophorese Forum’97, Strassburg, France, 1997; p. 59.
[110]
Harnisch, S.; Buszello, K.; Müller, B.W.; Müller, R.H. Influence of the Composition of Oil in Water Emulsions on the Pattern of Adsorbed Plasma Proteins. In Proceedings of 2nd World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Paris, France, 1998.
[111]
Jeppson, R.; R？ssner, S. The influence of emulsifying agents and of lipid soluble drugs on the fractional removal rate of lipid emulsions from the blood stream of the rabbit. Acta Pharmacol. Toxicol. 1975, 37, 134–144, doi:10.1111/j.1600-0773.1975.tb00830.x.
[112]
Yang, S.C.; Benita, S. Enhanced adsorption and drug targeting by positively charged submicron emulsions. Drug Dev. Res. 2000, 50, 476–486, doi:10.1002/1098-2299(200007/08)50:3/4<476::AID-DDR31>3.0.CO;2-6.
[113]
Klang, S.H.; Parnas, M.; Benita, S. Emulsions as drug carriers-possibilities, limitations, and future perspectives. In Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs; Müller, R.H., Benita, S., B？hm, H.L., Eds.; Medpharm: Stuttgart, Germany, 1998; pp. 31–65.
[114]
Korner, D.; Benita, S.; Albrecht, G.; Baszkin, A. Surface properties of mixed phospholipid–stearylamine monolayers and their interaction with a non-ionic surfactant (poloxamer). Colloids Surf. B Biointerfaces 1994, 3, 101–109, doi:10.1016/0927-7765(93)01111-4.
[115]
Tamilvanan, S.; Schmidt, S.; Müller, R.H.; Benita, S. In vitro adsorption of plasma proteins onto the surface (charges) modified-submicron emulsions for intravenous administration. Eur. J. Pharm. Biopharm. 2005, 59, 1–7, doi:10.1016/j.ejpb.2004.07.001.
[116]
Chyle, M.; Chyle, P. Affecting the immunity response with deoxycholic acid. Sb Lek. 1982, 84, 212–218.
[117]
Chyle, M.; Chyle, P. Deoxycholic acid in the therapy of herpes labialis (author’s transl). Cas. Lek. Cesk. 1975, 114, 1226–1229.
[118]
Fassati, P.; Chyle, P.; Fassati, M.; Chyle, M. Deoxycholic acid in the therapy of liver cirrhosis (author’s transl). Cas. Lek. Cesk. 1975, 114, 1222–1226.
[119]
Müller, R.H. Dispersions for the formulation of slightly or poorly soluble agents. DE10036871.9, 2001.
[120]
Müller, R.H.; Schmidt, S.; Buttle, I.; Akkar, A.; Schmitt, J.; Bromer, S. SolEmuls-novel technology for the formulation of IV emulsions with poorly soluble drugs. Int. J. Pharm. 2004, 269, 293–302, doi:10.1016/j.ijpharm.2003.09.019.
[121]
Janknegt, R.; de Marie, S.; Bakker-Woudenberg, I.A.; Crommelin, D.J. Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics. Clin. Pharmacokinet. 1992, 23, 279–291, doi:10.2165/00003088-199223040-00004.
[122]
Edwards, J.E.; Brouwer, K.R.; McNamara, P.J. GF120918, a P-glycoprotein modulator, increases the concentration of unbound amprenavir in the central nervous system in rats. Antimicrob. Agents Chemother. 2002, 46, 2284–2286, doi:10.1128/AAC.46.7.2284-2286.2002.
[123]
Kambara, T.; Inada, T.; Kubo, K.; Shingu, K. Propofol suppresses prostaglandin E (2) production in human peripheral monocytes. Immunopharmacol. Immunotoxicol. 2009, 31, 117–126, doi:10.1080/08923970802452046.
[124]
Washington, C.; Davis, S.S. Ageing effects in parenteral fat emulsions: the role of fatty acid. Int. J. Pharm. 1987, 39, 33–37, doi:10.1016/0378-5173(87)90195-5.
[125]
Schmidt, S.; Gessner, A.; Müller, R.H. Comparison of plasma protein adsorption patterns on emulsions for parenteral nutrition dependent to their age. In Proceedings of International Symposium on Controlled Release and Bioactive Materials, San Diego, CA, USA, 2011.
[126]
Schmidt, S.; Müller, R.H. Biological long-term stability of i. v. emulsions: Plasma protein adsorption on propofol-loaded emulsions. In Proceedings of 4th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Florence, Italy, 2002.
[127]
Müller, R.H.; Lück, M.; Kreuter, J. Arzneistofftr？gerpartikel für die gewebsspezifische Arzneistoffapplikation. DE19745950A1 , 1997.
