Drug Targeting Organ-Specific Strategies

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308 11 Development of Proteinaceous Drug Targeting Constructs [140] Park E, Starzyk RM, McGrath JP, Lee T, George J, Schutz AJ, Lynch P, Putney SD, J. Drug Target. 1998, 6, 53–64. [141] Ali SA, Joao HC, Hammerschmid F, Eder J, Steinkasserer A, J. Biol. Chem. 1999, 274, 24066–24073. [142] Finkelstein AV, Curr. Opin. Struct. Biol. 1997, 7, 60–71. [143] Pierschbacher MD, Ruoslahti E, Nature 1984, 309, 30–33. [144] Villaverde A, Feliu JX, Aris A, Harbottle RP, Benito A, Coutelle C, Biotechnol. Bioeng. 1998, 59, 294–301. [145] Reynolds P, Dmitriev I, Curiel D, Gene Ther. 1999, 6, 1336–1339. [146] Lin YZ, Yao SY, Hawiger J, J. Biol. Chem. 1996, 271, 5305–5308. [147] Zhang L, Torgerson TR, Liu XY, Timmons S, Colosia AD, Hawiger J, Tam JP, Proc. Natl Acad. Sci. USA 1998, 95, 9184–9189. [148] Rojas M, Donahue JP, Tan Z, Lin Y-Z, Nature Biotechnol. 1998, 16, 370–375. [149] Blanke SR, Milne JC, Benson EL, Collier RJ, Proc. Natl Acad. Sci. USA 1996, 93, 8437–8442. [150] Schwarze SR, Dowdy SF, Trends Pharmacol. Sci. 2000, 21, 45–48. [151] Penichet ML, Kang YS, Pardridge WM, Morrison SL, Shin SU, J. Immunol 1999, 163, 4421–4426. [152] McDevitt TC, Nelson KE, Stayton PS, Biotechnol. Prog. 1999, 15, 391–396. [153] Sano T, Cantor CR, Biotechnology (NY) 1991, 9, 1378–1381. [154] Ohno K, Levin B, Meruelo D, Biochem .Mol. Med. 1996, 58, 227–233.
12 Use of Human Tissue Slices in Drug Targeting Research Peter Olinga, Geny M. M. Groothuis 12.1 Introduction Drug Targeting Organ-Specific Strategies. Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) It has long been recognized that in vitro research can provide valuable information on basic mechanisms with respect to kinetics and efficacy of drug targeting concepts. Such in vitro research includes the use of isolated cells, cell lines and perfused organs. In this chapter the introduction of tissue slices into drug targeting research will be discussed.A brief history of the slice technique will first be given. Until now most research on the slice technique has been focused on the metabolism and transport of drugs and this topic will therefore be summarized before embarking on a discussion of the contribution of the tissue slice technique to the area of drug targeting research. In vitro research began with organ culture of embryonic organ rudiments [1]. The slice technique, using slices of tumour and liver tissue, was performed as early as 1923 by Otto Warburg [2] and in the following years by H. A. Krebs [3], who investigated the metabolism of amino acids in liver slices of cats, dogs and rats. These liver slices were prepared manually with limited reproducibility and viability [4].After a decline in the application of slices in liver research in favour of the use of isolated hepatocytes as well as isolated perfused liver preparation, the development of the Krumdieck slicer in the 1980s led to a ‘comeback’ of the technique enabling the production of reproducible and viable liver slices [5].This technology induced a renaissance of the slice technology.The development of these in vitro preparations has been of paramount importance for research on human liver function. As most of the research with tissue slices concerned the liver, this chapter will focus on the use of liver as the target tissue and only briefly mention the use of slices from other tissues in the concluding section of the chapter. The most abundant cell type in the liver is the hepatocyte, other cells in the liver are the non-parenchymal cells: Kupffer cells, the resident macrophages of the liver, endothelial cells and stellate cells. These cells have been discussed in more detail in Chapter 4. Since a high yield isolation procedure of rat hepatocytes was described in 1969 [6], hepatocytes have become the model of choice for drug transport studies in the liver in vitro [7]. With this procedure, isolated hepatocytes from many species have been prepared, including hepatocytes from rat, mouse, chicken, dog, fish, hamster, pig, cow, sheep and monkey liver (for an extensive review see reference [8]). Before 1976, only relatively small numbers of human hepatocytes could be isolated, due to the use of non-perfusion techniques [9]. Bojar et al. [10] were the first to use a perfusion technique on human livers which greatly enhanced the yield of hepatocytes. In principle the procedure that is now commonly used, is based on the one described by Seglen [6] for rat hepatocytes. Either a biopsy wedge with intact capsula on
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Preface Drug Targeting Organ-Specif
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Foreword Drug Targeting Organ-Speci
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X List of Contributors Henderik W.
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XII List of Contributors Grietje Mo
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Contents Drug Targeting Organ-Speci
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Contents XVII 3 Pulmonary Drug Deli
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Contents XIX 5.2.1.6 Identification
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Contents XXI 7.5 In Vitro Technique
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Contents XXIII 9.4 Tumour Vasculatu
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Contents XXV 12.8. Tissue Slices fr
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Dexa dexamethasone DIVEMA divinyl e
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LRP lung resistance related protein
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ROS reactive oxygen species RSV res
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Index a ADEPT 217, 224, 268, 291 ad
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e E. coli expression system 292 eff
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polymers, soluble 4, 218 - dendrime
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2 1 Drug Targeting: Basic Concepts
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24 2 Brain-Specific Drug Targeting
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54 3 Pulmonary Drug Delivery: Deliv
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4 Cell Specific Delivery of Anti-In
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The sinusoids are lined by the disc
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4.2.2.2 Phagocytosis and Transcytos
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ther inflammatory cells or accessor
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4.3 Hepatic Inflammation and Fibros
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process is not yet available. Sever
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this carrier to the KCs.When the ma
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e taken up rapidly by mannose recep
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y the transcriptional regulatory pr
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4.8 Testing Liver Targeting Prepara
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4.8 Testing Liver Targeting Prepara
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4.9 Targeting of Anti-inflammatory
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4.9 Targeting of Anti-inflammatory
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with monoclonal and bispecific anti
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References 117 [50] Coleman DL, Eur
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References 119 [133] Cronstein BN,
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5 Delivery of Drugs and Antisense O
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5.1 Introduction 123 convoluted tub
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treatment of the targeted cell and
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CL uptake (ml/min/g) centration pro
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5.2.1.4 Specific Binding of Alkylgl
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5.2 Renal Delivery Using Pro-Drugs
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5.2 Renal Delivery Using Pro-Drugs
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5.3 Renal Delivery Using Macromolec
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5.4 Renal Delivary of Antisense Oli
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5.4 Renal Delivery of Antisense Oli
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5.4.8 Benefits and Limitations of A
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via reabsorption from the luminal s
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References 153 [66] Franssen EJF, M
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References 155 [145] Van Zwieten PA
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158 6 A Practical Approach in the D
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172 7 Vascular Endothelium in Infla
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8 Strategies for Specific Drug Targ
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8.2.2 Histogenesis The traditional
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may become obstructed and compresse
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8.5 Strategies to Deliver Drugs to
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8.5 Strategies to Deliver Drugs to
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larly cytotoxic immune effector cel
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contributes to limited tumour penet
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ples onto anti-EGP-2 scFv. Biologic
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In the case of drug-monoclonal anti
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cells, the presence of co-stimulato
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Monomethoxy-polyethylene glycol CH
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e efficiently loaded into the lipos
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8.6 Clinical Studies 223 Table 8.5.
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8.6.3 (Synthetic) (co)Polymers Solu
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8.8 Conclusions and Future Perspect
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References 229 [43] Chaouchi NA, Va
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References 231 [126] Czuczman MS, G
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234 9 Tumour Vasculature Targeting
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360 13 Pharmacokinetic/Pharmacodyna
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372 14 Drug Targeting Strategy: Scr
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