Abstract
In an effort to develop novel strategies for delivery of drug candidates arising from rational drug design and recombinant DNA technology, pharmaceutical scientists have begun to employ the techniques of cell culture to study drug transport and metabolism at specific biological barriers. This review describes some of the general factors that should be considered in developing a cell culture model for transport studies and metabolism studies. In addition, we review in detail the recent progress that has been made in establishing, validating, and using cell cultures of epithelial barriers (e.g., cells that constitute the intestinal, rectal, buccal, sublingual, nasal, and ophthalmic mucosa as well as the epidermis of the skin) and the endothelial barriers (e.g., brain microvessel endothelial cells).
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REFERENCES
G. R. Marshall. Annu. Rev. Pharmacol. Toxicol. 27:193–213 (1987).
E. Tomlinson. Adv. Drug Del. Res. 1:87–198 (1987).
D. Blohm, C. Bollschweiler, and H. Hillen. Angew. Chem. Int. Ed. Engl. 27:207–225 (1988).
V. H. L. Lee (ed.). Peptide and Protein Drug Delivery: Fundamentals and Technology, Marcel Dekker, New York, 1990.
G. Wilson, S. S. Davis, and L. Illum (eds.). Pharmaceutical Applications of Cell and Tissue Culture, Plenum, New York, 1990.
M. V. Shah, K. L. Audus, and R. T. Borchardt. Pharm. Res. 6:624–627 (1989).
I. J. Hidalgo, K. M. Hillgren, G. M. Grass, and R. T. Borchardt. Pharm. Res. 6:S-114 (abstr PD950) (1989).
I. J. Hidalgo, K. M. Hillgren, G. M. Grass, and R. T. Borchardt. Submitted for publication.
A. B. Cairnie, L. F. Lamerton, and G. G. Steel. Exp. Cell Res. 39:528–538 (1965).
A. B. Cairnie, L. F. Lamerton, and G. G. Steel. Exp. Cell Res. 39:539–553 (1965).
J. Madara and S. S. Trier. In L. R. Johnson (ed.), Physiology of the Gastrointestinal Tract, Raven, New York, 1987, Vol. 2, pp. 1209–1249.
B. G. Munck. In L. R. Johnson (ed.), Physiology of the Gastrointestinal Tract, Raven, New York, 1981, Vol. 2, pp. 1097–1122.
H. Murer and R. Kinne. J. Membr. Biol. 55:61–95 (1980).
L. M. Pinkus. In W. B. Jakoby (ed.), Methods in Enzymology, Academic Press, New York, 1981, pp. 154–162.
M. Weiser. J. Biol. Chem. 248:2536–2541 (1973).
I. Osiecka, P. A. Porter, R. T. Borchardt, J. A. Fix, and C. R. Gardner. Pharm. Res. 2:284–289 (1985).
G. Henle and F. Deinhardt. J. Immunol. 79:54–59 (1957).
L. Lichtenberger, L. R. Miller, D. N. Erwin, and L. R. Johnson. Gastroenterology 65:242–251 (1973).
F. Raul, M. Kedinger, P. Simon, J. Grenier, and K. Haffen. Biol. Cell 33:163–168 (1978).
A. Quaroni, J. Wands, R. L. Trelstad, and K. J. Isselbacher. J. Cell Biol. 80:248–265 (1979).
Y. S. Chung, I. S. Song, R. H. Erickson, M. H. Sleisenger, and Y. S. Kim. Cancer Res. 45:2976–2982 (1985).
J. Fogh and G. Trempe. In J. Fogh (ed.), Human Tumor Cells in Vitro, Plenum, New York, 1975, pp. 115–141.
J. Fogh, J. M. Fogh, and T. Orfeo. J. Natl. Cancer Inst. 59:221–225 (1977).
M. Pinto, M.-D. Appay, P. Simon-Assmann, G. Chevalier, N. Dracopoli, J. Fogh, and A. Zweibaum. Biol. Cell 44:193–196 (1982).
M. Pinto, S. Robine-Leon, M.-D. Appay, M. Kedinger, N. Triadou, E. Dussaulx, B. Lacroix, P. Simon-Assmann, K. Haffen, J. Fogh, and A. Zweibaum. Biol. Cell 47:323–330 (1983).
M. Rousset. Biochimie 68:1035–1040 (1986).
A. Zweibaum, M. Pinto, G. Chevalier, E. Dussaulx, N. Triadou, B. Lacroix, K. Haffen, J.-L. Brun, and M. Rousset. J. Cell Physiol. 122:21–29 (1985).
M. Rousset, M. Laburthe, M. Pinto, G. Chevalier, C. Rouyer-Fesard, E. Dussaulx, G. Trugnan, N. Boige, J.-L. Brun, and A. Zweibaum. J. Cell Physiol. 123:377–385 (1985).
E. Grasset, M. Pinto, E. Dussaulx, A. Zweibaum, and J.-F. Desjeux. Am. J. Physiol. 247:C260–C267 (1984).
A. Zweibaum, N. Triadou, M. Kedinger, C. Augeron, S. Robine-Leon, M. Pinto, M. Rousset, and K. Haffen. Int. J. Cancer 32:407–412 (1983).
A. Le Bivic, M. Hirn, and H. Reggio. Proc. Natl. Acad. Sci. USA 85:136–140 (1988).
I. J. Hidalgo, T. J. Raub, and R. T. Borchardt. Gastroenterology 96:736–749 (1989).
T. E. Phillips, T. L. Phillips, and M. Neutra. Cell Tissue Res. 247:547–554 (1987).
I. J. Hidalgo and R. T. Borchardt. Pharm. Res. 5:S220 (abstr.) (1988).
J. A. Barnard and F. K. Ghishan. Gastroenterology 93:925–933 (1987).
F. A. Wilson and J. M. Dietschy. J. Clin. Invest. 51:3015–3025 (1972).
I. J. Hidalgo, A. Kato, and R. T. Borchardt. Biochem. Biophys. Res. Commun. 160:317–324 (1989).
P. A. Gonella, K. Siminoski, R. A. Murphy, and M. R. Neutra. J. Clin. Invest. 80:22–32 (1987).
R. Muthiah and B. Seetharam. J. Cell Biol. 105:235A (abstr.) (1987).
T. E. Hughes, W. V. Sasak, J. M. Ordovas, T. M. Forte, S. Lamon-Fava, and E. J. Schaefer. J. Biol. Chem. 262:3762–3767 (1987).
M. G. Traber, H. J. Kayden, and M. J. Rindler. J. Lipid Res. 28:1350–1363 (1987).
C. L. Pryor and R. T. Borchardt. Biophys. J. 55:158 (abstr. MPos251) (1989).
J. L. Madara. J. Clin. Invest. 83:1089–1094 (1989).
J. L. Madara. Cell 53:497–498 (1988).
J. L. Madara and J. Stafford. J. Clin. Invest. 83:724–727 (1989).
J. L. Madara, D. Barenberg, and S. Carlson. J. Cell Biol. 102:2125–2136 (1986).
J. R. Pappenheimer and K. Z. Reiss. J. Membr. Biol. 100:123–136 (1987).
J. L. Madara and J. R. Pappenheimer. J. Membr. Biol. 100:149–164 (1987).
R. T. Borchardt, I. J. Hidalgo, K. M. Hillgren, and M. Hu. In G. Wilson, S. J. Davis, and L. Illum (eds.), Pharmaceutical Applications of Cell and Tissue Culture, Plenum Press, New York (in press).
J. A. Fix. J. Control. Rel. 6:151–156 (1987).
H. P. Hauri, E. E. Sterchi, D. Bienz, J. Fransen, and A. Marxer. J. Cell Biol. 101:838–851 (1985).
T. H. Wilson. Intestine Absorption, W.B. Saunders, Philadelphia, 1962.
A. G. de Boer and D. D. Breimer. In L. F. Prescott and W. S. Nimmo (eds.), Drug Absorption, Adis Press, Sydney, 1979, p. 61.
D. J. A. Crommelin, J. Modderkolk, and C. J. de Blay. Int. J. Pharm. 3:299–309 (1979).
T. Nishihata, J. H. Rytting, and T. Higuchi. J. Pharm. Sci. 71:869–872 (1982).
T. Nishihata, J. H. Rytting, A. Kamada, T. Higuchi, M. Routh, and L. Caldwell. J. Pharm. Pharmacol. 35:148–151 (1983).
J. H. Rytting. In V. H. L. Lee (ed.), Peptide, and Protein Drug Delivery, Marcel Dekker, New York, 1990.
A. C. Moffat. Top. Med. Chem. 4:1–26 (1971).
C. A. Squier and N. W. Johnson. Br. Med. Bull. 31:169–175 (1975).
D. Adams. Arch. Oral Biol. 19:865–872 (1974).
W. R. Galey, H. K. Lonsdale, and S. Nacht. J. Invest. Dermatol. 67:713–717 (1976).
C. A. Squier and B. K. Hall. J. Invest. Dermatol. 84:176–179 (1985).
P. J. Polverini and D. B. Solt. Lab. Invest. 54:432–441 (1986).
D. Arenholt-Bindslev, A. Jepsen, D. K. MacCallum, and J. H. Lillie. J. Invest. Dermatol. 88:314–319 (1987).
D. Arenholt-Bindslev, P. Horsted-Bindslev, and H. P. Philipsen. Scand. J. Dent. Res. 95:467–474 (1987).
M. R. Tavakoli-Saberi and K. L. Audus. Pharm. Res. 6:160–166 (1989).
W. R. Galey, H. K. Lonsdale, and S. Nacht. J. Invest. Dermatol. 67:713–717 (1976).
C. A. Squier and B. K. Hall. J. Invest. Dermatol. 84:176–179 (1985).
K. Tolo and J. Jonsen. Arch. Oral Biol. 26:419–422 (1975).
C. A. Squier. J. Ultrastruct. Res. 43:160–177 (1973).
P. P. H. Le Brun, P. L. A. Fox, M. E. De Vries, and H. E. Bodde. Int. J. Pharm. 49:141–145 (1989).
Y. Kurosaki, N. Aya, Y. Okada, T. Nakayama, and T. Kimura. J. Pharmacobio-Dyn. 9:287–296 (1986).
M. R. Tavakoli-Saberi and K. L. Audus. Int. J. Pharm. 56:135–142 (1989).
M. R. Tavakoli-Saberi, A. Williams, and K. L. Audus. Pharm. Res. 6:5197 (abstr. PP1474) (1989).
R. E. Stratford, Jr., and V. H. L. Lee, Int. J. Pharm. 30:73–82 (1986).
K. S. E. Su. Pharm. Int. 7:8–11 (1986).
W. A. Lee and J. P. Longenecker. Biopharm. Manufact. 1:30–37 (1988).
B. W. Jafek. Laryngoscope 93:1576–1599 (1983).
B. Petruson, H.-A. Hansson, and G. Karlsson. Arch. Otolaryngol. 110:576–581 (1984).
E. B. Brittebo, A. Castonguay, K. Furuya, and S. S. Hecht. Cancer Res. 43:4343–4348 (1983).
J. M. Wiesel, H. Gamiel, I. Vlodavsky, I. Gay, and H. Ben-Bassat. Eur. J. Clin. Invest. 13:57–63 (1983).
D. L. Newton, W. R. Henderson, and M. B. Sporn. Cancer Res. 40:3413–3425 (1980).
A. A. J. L. Rutten, R. B. Beems, J. W. G. M. Wilmer, and V. J. Feron. In Vitro Cell. Dev. Biol. 24:931–935 (1988).
V. E. Steele and J. T. Arnold. In Vitro Cell. Dev. Biol. 21:681–687 (1985).
R. Wu, J. Yankasas, E. Cheng, M. R. Knowles, and R. Boucher. Am. Rev. Resp. Dis. 132:311–320 (1985).
J. R. Yankaskas, C. U. Cotton, M. R. Knowles, J. T. Gatzy, and R. C. Boucher. Am. Rev. Resp. Dis. 132:1281–1287 (1985).
M. Ohnishi, J. Ruhno, J. Bienenstock, J. Dolovich, and J. A. Denberg. J. Allergy Clin. Immunol. 83:1091–1100 (1989).
G. D. Stoner, Y. Katoh, J. M. Fvidart, G. A. Myers, and C. C. Harris. Methods Cell Biol. 21A:15–35 (1980).
J. F. Lechner, A. Haugen, H. Autrup, Z. A. McClendon, B. F. Trump, and C. C. Harris. Cancer Res. 41:2294–2304 (1981).
J. H. Widdicombe, C. B. Basbaum, and E. Highland. Am. J. Physiol. 241:C184–C192 (1981).
A. T. Mariassy, C. G. Plopper, J. A. St. George, and D. W. Wilson. Anat. Rec. 222:49–59 (1988).
N. Schoppa, S. R. Shorofsky, F. Jow, and D. J. Nelson. J. Membr. Biol. 108:73–90 (1989).
D. L. Coleman, I. K. Tuet, and J. H. Widdicombe, Am. J. Physiol. 246:C355–C359 (1984).
N. J. Willumsen, C. W. Davis, and R. C. Boucher. Am. J. Physiol. 256:C1033–C1044 (1989).
N. J. Willumsen, C. W. Davis, and R. C. Boucher. Am. J. Physiol. 256:C1045–C1053 (1989).
N. J. Willumsen and R. C. Boucher. Am. J. Physiol. 256:C1054–C1063 (1989).
A. T. Hood, D. Currie, and S. J. Garte. In Vitro Cell. Dev. Biol. 23:274–278 (1987).
K. A. Holbrook and H. Hennings. J. Invest. Dermatol. 81:11s–24s (1983).
P. B. Medawar. Nature 148:783 (1941).
H. Green, O. Kehincle, and J. Thomas. Proc. Natl. Acad. Sci. USA 76:5665–5668 (1979).
C. Walzer, M. Benathan, and E. Frenk. J. Invest. Dermatol. 92:78–81 (1989).
T.-T. Sun and H. Green. J. Biol. Chem. 253:2053–2060 (1978).
P. M. Steinert and S. H. Yuspa. Science 200:1491–1493 (1978).
E. Fuchs and H. Green. Cell 19:1033–1042 (1980).
T. I. Doran, A. Vidrich, and T.-T. Sun. Cell 22:17–25 (1980).
M. L. Williams, S. L. Rutherford, M. Ponec, M. Hincenbergs, D. R. Placzek, and P. M. Elias. J. Invest. Dermatol. 91:86–91 (1988).
M. Ponec, J. Kempenaar, and J. Boonstra. Biochim. Biophys. Acta 921:512–521 (1987).
M. L. Williams, S. L. Rutherford, M. Ponec, M. Hincenbergs, D. R. Placek, and P. M. Elias. J. Invest. Dermatol. 91:86–91 (1988).
F. Vaughan, R. H. Gray, and I. A. Bernstein. In Vitro Cell. Dev. Biol. 22:141–149 (1986).
K. C. Madison, D. C. Swartzendruber, P. W. Wertz, and D. T. Downing. J. Invest. Dermatol. 90:110–116 (1988).
M. L. Williams, B. E. Brown, D. J. Monger, S. Grayson, and P. M. Elias. J. Cell. Physiol. 136:103–110 (1988).
E. Bell, B. Ivarssen, and C. Merrill. Science 211:1042–1054 (1979).
E. Bell, S. Sher, B. Huss, C. Merrill, S. Rosen, A. Chamson, D. Asselineau, L. Dubertret, B. Coulomb, C. Lapiere, G. Nusgens, and Y. Neveux. J. Invest. Dermatol. 81:2s–10s (1983).
M. Regnier, M. Prunieras, and D. Woodley. Front. Matrix Biol. 9:4–35 (1981).
M. Prunieras, M. Regnier, and D. Woodley. J. Invest. Dermatol. 81:28s–33s (1983).
G. M. Gray and H. S. Yardley. J. Lipid Res. 16:441–447 (1975).
M. A. Lampe, A. L. Burlingame, J. O. Witney, M. L. Williams, B. E. Brown, E. Roitman, and P. M. Elias. J. Lipid Res. 24:120–130 (1983).
M. A. Lampe, M. L. Williams, and P. M. Elias. J. Lipid Res. 24:131–140 (1983).
R. M. Lavker. J. Ultrastruct. Res. 55:79–86 (1976).
A. F. Hayward. Cell Tissue Res. 187:323–331 (1978).
L. Landmann. J. Invest. Dermatol. 87:202–209 (1986).
P. M. Elias and D. S. Friend. J. Cell Biol. 65:180–191 (1975).
P. M. Elias and B. E. Brown. Lab. Invest. 39:574–583 (1978).
H. S. Hansen and B. Jensen. Biochim. Biophys. Acta 834:357–363 (1986).
J. L. Melton, P. W. Wertz, D. C. Swartzendruber, and D. T. Downing. Biochim. Biophys. Acta 921:191–197 (1987).
L. Landmann. Anat. Embryol. 178:1–13 (1988).
K. C. Madison, D. C. Swartzendruber, P. W. Wertz, and D. T. Downing. J. Invest. Dermatol. 93:10–17 (1989).
R. L. Bartel and R. T. Borchardt. Pharm. Res. 5:S-79 (abstr. PD828) (1988).
D. T. Woodley, T. Kalebee, A. J. Banes, W. Link, M. Prunieras, and L. Liotta. J. Invest. Dermatol. 86:418–423 (1986).
M. B. Cumpstone, A. H. Kennedy, C. S. Harmon, and R. O. Potts. J. Invest. Dermatol. 92:597–600 (1989).
V. H. W. Mak, M. B. Cumpstone, A. H. Kennedy, C. S. Harmon, R. H. Guy, and R. O. Potts. J. Invest. Dermatol. 92:475 (1989).
M. Ponec. Personal communication.
M. Regnier, J. Schweizer, S. Michel, C. Bailly, and M. Prunieras. Exp. Cell Res. 165:63–72 (1986).
F. Grinnell, K.-I. Toda, and C. Lamke-Seymour. Exp. Cell Res. 172:439–449 (1987).
M. Regnier, C. Desbas, C. Bailly, and M. Darmon. In Vitro Cell. Dev. Biol. 24:625–632 (1988).
M. Ponec, A. Weerheim, J. Kempenaar, A. M. Mommaas, and D. H. Nugteren. J. Lipid Res. 29:949–961 (1988).
J. G. Rheinwald and H. Green. Cell 6:331–344 (1975).
F. Vaughan, R. H. Gray, and I. A. Bernstein. In Vitro Cell. Dev. Biol. 22:141–149 (1986).
F. Vaughan, S. Zaman, R. Scavarelli, and I. A. Bernstein. J. Toxicol. Environ. Health 23:507–518 (1988).
G. Theall, M. Eisinger, and D. Grunberger. Carcinogenesis 2:581–587 (1981).
D. R. Bickers, C. L. Marcelo, T. Dutta-Choudhury, and H. Mukhtar. J. Pharmacol. Exp. Ther. 223:163–168 (1982).
J. DiGiovanni, D. R. Miller, J. M. Singer, A. Viaje, and T. J. Slaga. Cancer Res. 42:2579–2586 (1982).
M. Mukhtar, B. J. DelTito, C. L. Marcelo, M. Das, and D. R. Bickers. Carcinogenesis 5:1565–1571 (1984).
M. Das, H. Mukhtar, B. J. DelTito, C. L. Marcelo, and D. R. Bickers. J. Invest. Dermatol. 87:4–9 (1986).
P. K. Shah and R. T. Borchardt. Pharm. Res. 5:S-188 (abstr. PP1357) (1988).
P. K. Shah and R. T. Borchardt. Pharm. Res. 6:5–148 (abstr. PO1085) (1989).
V. H. L. Lee. Pharm. Int. 6:135–138 (1985).
V. H. L. Lee. Pharm. Technol. 11:26–38 (1987).
T. Kuwabara. In L. Weiss (ed.), Histology, Elsevier Biomedical, New York, 1983, pp. 1134–1176.
W. H. Havener. Ocular Pharmacology, C. V. Mosby, St. Louis, 1983, pp. 18–43.
F. W. Stocker, A. Eiring, R. Georgiade, and N. Georgiade. Am. J. Ophthalmol. 46:294–298 (1958).
L. Xie and B. M. Gebhardt. In Vitro Cell. Dev. Biol. 25:20–22 (1989).
I. K. Gipson and S. M. Grill. Invest. Ophthalmol. Vis. Sci. 23:269–273 (1982).
K. Y. Chan. Curr. Eye Res. 5:357–362 (1986).
S. J. Simmons, M. M. Jumblatt, and A. H. Neufeld. Toxicol. Appl. Pharmacol. 88:13–23 (1987).
R. S. Beach and M. C. Kenney. Biochem. Biophys. Res. Commun. 108:904–909 (1982).
P. Hsieh and J. Baum. Invest. Ophthalmol. Vis. Sci. 26:457–463 (1985).
J. R. Samples, S. K. Nayak, C. Gualtieri, and P. S. Binder. Exp. Eye Res. 41:487–495 (1985).
D. R. Whikehart, B. Montgomery, and L. M. Hafer. Curr. Eye Res. 6:709–717 (1987).
K. Engelmann, M. Bohnke, and P. Friedl. Invest. Ophthalmol. Vis. Sci. 29:1656–1662 (1988).
M. Y. Pistov, E. Y. Sadovnikova, and S. M. Danilov. Exp. Eye Res. 47:403–414 (1988).
B. Y. J. T. Yue, J. Sugar, J. E. Gilboy, and J. L. Elvart. Invest. Ophthalmol. Vis. Sci. 30:248–253 (1989).
J. R. Samples, P. S. Binder, and S. Nayak. Exp. Eye Res. 49:1–12 (1989).
T.-T. Sun and H. Green. Nature 269:489–492 (1977).
M. M. Jumblatt and A. H. Neufeld. Invest. Ophthalmol. Vis. Sci. 24:1139–1143 (1983).
M. M. Jumblatt and A. H. Neufeld. Invest. Ophthalmol. Vis. Sci. 27:8–13 (1986).
A. Klausner. Bio/Technology 5:779–786 (1987).
M. Perlman and J. L. Baum. Arch. Ophthalmol. 92:238–239 (1974).
D. R. Whikehart and R. T. Fletcher. Exp. Eye Res. 28:285–288 (1979).
N. A. Panjwani and J. Baum. Invest. Ophthalmol. Vis. Sci. 26:450–456 (1985).
G. E. Palade. Simionescu. In N. Simionescu and M. Simionescu (eds.), Endothelial Cell Biology in Health and Disease, Plenum Press, New York, 1988, pp. 3–22.
M. Siminoescu. In N. Simionescu and M. Simionescu (eds.), Endothelial Cell Biology in Health and Disease, Plenum Press, New York, 1988, pp. 69–104.
M. W. Brightman. In E. A. Neuwelt (ed.), Implications of the Blood-Brain Barrier and Its Manipulation, Vol. 1, Plenum Medical, New York, 1989, pp. 53–83.
E. M. Renkin. In N. Simionescu and M. Simionescu (eds.), Endothelial Cell Biology in Health and Disease, Plenum Press, New York, 1988, pp. 51–68.
D. Z. Gerhart, M. A. Broderius, and L. R. Drewes. Brain Res. Bull. 21:785–793 (1988).
P. D. Bowman, S. R. Ennis, and K. E. Rarey. Ann. Neurol. 14:396–402 (1983).
I. E. Goetz, J. Warren, C. Estrada, E. Roberts, and D. N. Krause. In Vitro Cell. Dev. Biol. 21:172–180 (1985).
K. L. Audus and R. T. Borchardt. Pharm. Res. 3:81–87 (1986).
K. L. Audus and R. T. Borchardt. Ann. N.Y. Acad. Sci. 507:9–18 (1987).
P. Phillips, P. Kumar, S. Kumar, and M. Waghe. J. Anat. 129:261–272 (1979).
L. E. DeBault, L. E. Kahn, S. P. Frommes, and P. A. Cancilla. In Vitro 15:473–487 (1979).
R. A. Robinson, C. J. TenEyck, and M. N. Hart. Lab. Invest. 54:579–588 (1986).
B. Dropulic and C. L. Masters. In Vitro Cell. Dev. Biol. 23:775–781 (1987).
U. Mischeck, J. Meyer, and H.-J. Galla. Cell Tissue Res. 256:221–226 (1989).
P. Panula, F. Joo, and L. Rechart. Experientia 34:95–97 (1978).
M. Spatz, J. Bembry, R. F. Dodson, H. Hervonen, and M. R. Murray. Brain Res. 191:577–582 (1980).
P. D. Bowman, A. L. Betz, D. Ar, J. S. Wolinsky, J. B. Penny, R. R. Shivers, and G. Goldstein. In Vitro 17:353–362 (1981).
S. K. Williams, J. F. Gillis, M. A. Matthews, R. C. Wagner, and M. W. Bitensky. J. Neurochem. 35:374–381 (1980).
F. Lasbennes and J. Gayet. Neurochem. Res. 9:1–10 (1984).
A. L. McCall, J. Valente, R. Cordero, N. B. Ruderman, and K. Tornhem. Microvasc. Res. 35:325–333 (1988).
L. E. DeBault and P. A. Cancilla. Science 207:653–655 (1980).
J.-H. Tao-Cheng, Z. Nagy, and M. W. Brightman. J. Neurosci. 7:3293–3299 (1988).
A. M. Trammel and R. T. Borchardt. Pharm. Res. 6:S-88 (abstr. PD847) (1989).
A. Orlidge and P. A. D'Amore. J. Cell Biol. 105:1455–1462 (1987).
Y. Sato and D. B. Rifkin. J. Cell Biol. 109:309–315 (1989).
A. Baranczyk-Kuzma, K. L. Audus, and R. T. Borchardt. J. Neurochem. 46:1956–1960 (1986).
A. Baranczyk-Kuzma, K. L. Audus, and R. T. Borchardt. Neurochem. Res. 14:689–691 (1989).
G. K. E. Scriba and R. T. Borchardt. J. Neurochem. 53:610–615 (1989).
A. Baranczyk-Kuzma and K. L. Audus. J. Cerebr. Blood Flow Metab. 7:801–805 (1987).
A. Baranczyk-Kuzma, T. J. Raub, and K. L. Audus. J. Cerebr. Blood Flow Metab. 9:280–289 (1989).
S. Rim, K. L. Audus, and R. T. Borchardt. Int. J. Pharm. 32:79–84 (1986).
M. V. Shah, K. L. Audus, and R. T. Borchardt. Pharm. Res. 6:624–627 (1989).
K. L. Audus. J. Control. Rel. 11:51–59 (1990).
K. L. Audus and R. T. Borchardt. J. Neurochem. 47:484–488 (1986).
A. M. Trammel and R. T. Borchardt. Pharm. Res. 4:S-41 (abstr. PD427) (1987).
M. V. Shah and R. T. Borchardt. Pharm. Res. 6:S-77 (abstr. 1852) (1989).
J. Greenwood, A. S. Hazell, and O. E. Pratt. J. Cerebr. Blood Flow Metab. 9:226–233 (1989).
J. M. B. B. van Bree, K. L. Audus, and R. T. Borchardt. Pharm. Res. 5:369–371 (1988).
J. Chastain and R. T. Borchardt. Neurosci. Res. Commun. 4:147–152 (1989).
J. Chastain and R. T. Borchardt. J. Cell Biol. 105:3280 (abstr. 1852) (1987).
F. L. Guillot, K. L. Audus, and T. J. Raub. Microvasc. Res. 39:1–14 (1990).
T. J. Raub and K. L. Audus. J. Cell Biol. 105:312 (abstr. 1759) (1987).
B. T. Keller, K. R. Smith, and R. T. Borchardt. Pharm. Weekblad 10:38–39 (1988).
K. R. Smith and R. T. Borchardt. Pharm. Res. 6:466–473 (1989).
S. Raeissi and K. L. Audus. J. Pharm. Pharmacol. 41:848–852 (1989).
P. M. Reardon and K. L. Audus. Pharm. Res. 6:S-88 (abstr. PD845) (1989).
S. E. Thompson and K. L. Audus. Pharm. Res. 6:S-175 (abstr. PD1194) (1989).
C. R. Newton and T. J. Raub. J. Cell Biol. 107:770a (abstr. 4374) (1988).
J. M. B. B. van Bree, A. G. de Boer, J. C. Verhoef, M. Danhof, and D. D. Breimer. J. Pharmacol. Exp. Ther. 249:901–905 (1989).
M. Baba, R. Oishi, and K. Saeki. Naunyn-Schmiedeberg Arch. Pharmacol. 337:423–428 (1988).
F. L. Guillot and K. L. Audus. J. Cell Biol. 107:809a (abstr. 4601) (1988).
K. L. Audus and F. L. Guillot. J. Am. Inst. Chem. Eng. 00:000 (abstr.) (1989).
F. L. Guillot and K. L. Audus. Pharm. Res. 6:S-221 (abstr. PP1531) (1989).
F. L. Guillot and K. L. Audus. J. Cell Biol. 109:35a (abstr. 174) (1989).
K. R. Smith and R. T. Borchardt. Biochem. Biophys. Res. Commun. 157:300–314 (1988).
K. L. Audus, S. R. Holthaus, J. A. Shinogle, and J. M. B. B. van Bree. Res. Commun. Chem. Pathol. Pharmacol. 60:71–85 (1988).
K. L. Audus, J. A. Shinogle, S. R. Holthaus, and F. L. Guillot. Int. J. Pharm. 45:249–257 (1988).
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Audus, K.L., Bartel, R.L., Hidalgo, I.J. et al. The Use of Cultured Epithelial and Endothelial Cells for Drug Transport and Metabolism Studies. Pharm Res 7, 435–451 (1990). https://doi.org/10.1023/A:1015800312910
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DOI: https://doi.org/10.1023/A:1015800312910