Mechanistic analysis of chemical permeation enhancers for oral drug delivery

Pharmaceutical Research

Volumn 25, Issue 6, 2008, Pages 1412-1419

  Whitehead, Kathryn ^a   Mitragotri, Samir ^a  

^a University of California   (United States)

Author keywords

Caco 2; Mechanism; Oral drug delivery; Permeation enhancer; Transcellular

Indexed keywords

3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; AMPHOLYTE; LACTATE DEHYDROGENASE; PENETRATION ENHANCING AGENT; SULFONIC ACID DERIVATIVE; SURFACTANT;

ARTICLE; CELL STRAIN CACO 2; CELLULAR DISTRIBUTION; CHEMICAL ANALYSIS; DRUG DELIVERY SYSTEM; DRUG MECHANISM; ELECTRIC RESISTANCE; HUMAN; HUMAN CELL; HYDROPHILICITY; HYDROPHOBICITY; IN VITRO STUDY; INTESTINE MUCOSA PERMEABILITY; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; CACO-2 CELLS; DRUG DELIVERY SYSTEMS; ELECTRIC IMPEDANCE; HUMANS; INTESTINAL ABSORPTION; L-LACTATE DEHYDROGENASE; PERMEABILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 43049123064     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-008-9542-2     Document Type: Article

References (38)

1. 1. S. K. Kim D. Y. Lee E. Lee Y.-k. Lee C. Y. Kim H. T. Moon Y. Byun 2007 Absorption study of deoxycholic acid–heparin conjugate as a new form of oral anti-coagulant J. Control. Rel. 120 4 10 10.1016/j.jconrel.2007.03.008 1:CAS:528:DC%2BD2sXmt1GlsLo%3D S. K. Kim, D. Y. Lee, E. Lee, Y.-k. Lee, C. Y. Kim, H. T. Moon, and Y. Byun. Absorption study of deoxycholic acid–heparin conjugate as a new form of oral anti-coagulant. J. Control. Rel. 120:4–10 (2007).
2. 2. K. M. Wood G. Stone N. A. Peppas 2006 Lectin functionalized complexation hydrogels for oral protein delivery J. Control. Rel. 116 e66 e68 10.1016/j.jconrel.2006.09.053 1:STN:280:DC%2BD2srgtV2gsA%3D%3D K. M. Wood, G. Stone, and N. A. Peppas. Lectin functionalized complexation hydrogels for oral protein delivery. J. Control. Rel. 116:e66–e68 (2006).
3. 3. M. Goldberg I. Gomez-Orellana 2003 Challenges for the oral delivery of macromolecules Nat Rev. Drug. Discov. 2 289 295 12669028 10.1038/nrd1067 1:CAS:528:DC%2BD3sXisFWkt7s%3D M. Goldberg, and I. Gomez-Orellana. Challenges for the oral delivery of macromolecules. Nat. Rev. Drug. Discov. 2:289–295 (2003).
4. 4. B. J. Aungst 2000 Intestinal permeation enhancers J. Pharm. Sci. 89 429 442 10737905 10.1002/(SICI)1520-6017(200004)89:4<429::AID-JPS1>3.0.CO;2-J 1:CAS:528:DC%2BD3cXis12ktbw%3D B. J. Aungst. Intestinal permeation enhancers. J. Pharm. Sci 89:429–442 (2000).
5. 5. N. N. Salama N. D. Eddington A. Fasano 2006 Tight junction modulation and its relationship to drug delivery Adv. Drug. Deliv. Rev. 58 15 28 16517003 10.1016/j.addr.2006.01.003 1:CAS:528:DC%2BD28Xjs1WntLo%3D N. N. Salama, N. D. Eddington, and A. Fasano. Tight junction modulation and its relationship to drug delivery. Adv. Drug. Deliv. Rev. 58:15–28 (2006).
6. 6. D. Bourdet G. Pollack D. Thakker 2006 Intestinal absorptive transport of the hydrophilic cation ranitidine: A kinetic modeling approach to elucidate the role of uptake and efflux transporters and paracellular vs. transcellular transport in Caco-2 cells Pharm. Res. 23 1178 1187 16741656 10.1007/s11095-006-0204-y 1:CAS:528:DC%2BD28XmtFCntrY%3D D. Bourdet, G. Pollack, and D. Thakker. Intestinal absorptive transport of the hydrophilic cation ranitidine: A kinetic modeling approach to elucidate the role of uptake and efflux transporters and paracellular vs. transcellular transport in Caco-2 cells. Pharm. Res. 23:1178–1187 (2006).
7. 7. S. Maher L. Feighery D. Brayden S. McClean 2007 Melittin as an epithelial permeability enhancer I: Investigation of its mechanism of action in Caco-2 monolayers Pharm. Res. 24 1336 1345 17373574 10.1007/s11095-007-9288-2 1:CAS:528:DC%2BD2sXnt1Cksrk%3D S. Maher, L. Feighery, D. Brayden, and S. McClean. Melittin as an epithelial permeability enhancer I: Investigation of its mechanism of action in Caco-2 monolayers. Pharm. Res. 24:1336–1345 (2007).
8. 8. C. M. Meaney C. M. O’Driscoll 2000 A comparison of the permeation enhancement potential of simple bile salt and mixed bile salt: Fatty acid micellar systems using the Caco-2 cell culture model Int. J. Pharm. Sci. 207 21 30 10.1016/S0378-5173(00)00526-3 1:CAS:528:DC%2BD3cXosVGls74%3D C. M. Meaney, and C. M. O’Driscoll. A comparison of the permeation enhancement potential of simple bile salt and mixed bile salt: Fatty acid micellar systems using the Caco-2 cell culture model. Int. J. Pharm. Sci. 207:21–30 (2000).
9. 9. T. Shimazaki M. Tomita S. Sadahiro M. Hayashi S. Awazu 1998 Absorption-enhancing effects of sodium caprate and palmitoyl carnitine in rat and human colons Dig. Dis. Sci. 43 641 645 9539662 10.1023/A:1018835829643 1:CAS:528:DyaK1cXisVGisbg%3D T. Shimazaki, M. Tomita, S. Sadahiro, M. Hayashi, and S. Awazu. Absorption-enhancing effects of sodium caprate and palmitoyl carnitine in rat and human colons. Dig. Dis. Sci. 43:641–645 (1998).
10. 10. S. M. Merwe van der J. C. Verhoef J. H. M. Verheijden A. F. Kotze H. E. Junginger 2004 Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs Eur. J. Pharm. Biopharm. 58 225 235 15296951 10.1016/j.ejpb.2004.03.023 S. M. van der Merwe, J. C. Verhoef, J. H. M. Verheijden, A. F. Kotze, and H. E. Junginger. Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. Eur. J. Pharm. Biopharm. 58:225–235 (2004).
11. 11. A. C. Chao J. V. Nguyen M. Broughall J. Recchia C. R. Kensil P. E. Daddona J. A. Fix 1998 Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin J. Pharm. Sci. 87 1395 1399 9811496 10.1021/js9800735 1:CAS:528:DyaK1cXlsVelurc%3D A. C. Chao, J. V. Nguyen, M. Broughall, J. Recchia, C. R. Kensil, P. E. Daddona, and J. A. Fix. Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin. J. Pharm. Sci. 87:1395–1399 (1998).
12. 12. T. Suzuki H. Hara 2006 Difructose anhydride III and sodium caprate activate paracellular transport via different intracellular events in Caco-2 cells Life Sciences 79 401 410 16566947 10.1016/j.lfs.2006.01.044 1:CAS:528:DC%2BD28XltlKrtrY%3D T. Suzuki, and H. Hara. Difructose anhydride III and sodium caprate activate paracellular transport via different intracellular events in Caco-2 cells. Life Sciences 79:401–410 (2006).
13. 13. E. Duizer C. Wulp Van Der C. H. M. Versantvoort J. P. Groten 1998 Absorption enhancement, structural changes in tight junctions and cytotoxicity caused by palmitoyl carnitine in Caco-2 and IEC-18 cells J. Pharmacol. Exp. Ther. 287 395 402 9765361 1:CAS:528:DyaK1cXmvVWjsro%3D E. Duizer, C. Van Der Wulp, C. H. M. Versantvoort, and J. P. Groten. Absorption enhancement, structural changes in tight junctions and cytotoxicity caused by palmitoyl carnitine in Caco-2 and IEC-18 cells. J. Pharmacol. Exp. Ther. 287:395–402 (1998).
14. 14. S. Hess V. Rotshild A. Hoffman 2005 Investigation of the enhancing mechanism of sodium n-[8-(2-hydroxybenzoyl)amino]caprylate effect on the intestinal permeability of polar molecules utilizing a voltage clamp method Eur. J. Pharm. Sci. 25 307 312 15911227 1:CAS:528:DC%2BD2MXks1Git78%3D S. Hess, V. Rotshild, and A. Hoffman. Investigation of the enhancing mechanism of sodium n-[8-(2-hydroxybenzoyl)amino]caprylate effect on the intestinal permeability of polar molecules utilizing a voltage clamp method. Eur. J. Pharm. Sci. 25:307–312 (2005).
15. 15. T. Uchiyama T. Sugiyama Y. S. Quan A. Kotani N. Okada T. Fujita S. Muranishi A. Yamamoto 1999 Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: Their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside J. Pharm. Pharmacol. 51 1241 1250 10632081 10.1211/0022357991776976 1:CAS:528:DC%2BD3cXhslOnug%3D%3D T. Uchiyama, T. Sugiyama, Y. S. Quan, A. Kotani, N. Okada, T. Fujita, S. Muranishi, and A. Yamamoto. Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: Their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside. J. Pharm. Pharmacol. 51:1241–1250 (1999).
16. 16. P. Sharma M. V. S. Varma H. P. S. Chawla R. Panchagnula 2005 Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers Il Farmaco 60 870 873 16182296 10.1016/j.farmac.2005.08.006 1:CAS:528:DC%2BD2MXhtFyktrjO P. Sharma, M. V. S. Varma, H. P. S. Chawla, and R. Panchagnula. Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers. Il Farmaco. 60:870–873 (2005).
17. 17. A. A. Raoof Z. Ramtoola B. McKenna R. Z. Yu G. Hardee R. S. Geary 2002 Effect of sodium caprate on the intestinal absorption of two modified antisense oligonucleotides in pigs Eur. J. Pharm. Sci. 17 131 138 12393140 10.1016/S0928-0987(02)00162-8 1:CAS:528:DC%2BD38XotVerurc%3D A. A. Raoof, Z. Ramtoola, B. McKenna, R. Z. Yu, G. Hardee, and R. S. Geary. Effect of sodium caprate on the intestinal absorption of two modified antisense oligonucleotides in pigs. Eur. J. Pharm. Sci. 17:131–138 (2002).
18. 18. T. W. Leonard J. Lynch M. J. McKenna D. J. Brayden 2006 Promoting absorption of drugs in humans using medium-chain fatty acid-based solid dosage forms: GIPET Expert. Opin. Drug Deliv. 3 685 692 16948563 10.1517/17425247.3.5.685 1:CAS:528:DC%2BD28XovF2gur0%3D T. W. Leonard, J. Lynch, M. J. McKenna, and D. J. Brayden. Promoting absorption of drugs in humans using medium-chain fatty acid-based solid dosage forms: GIPET. Expert. Opin. Drug Deliv. 3:685–692 (2006).
19. 19. E. K. Anderberg T. Lindmark P. Artursson 1993 Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route Pharm. Res. 10 857 864 8321854 10.1023/A:1018909210879 1:CAS:528:DyaK3sXkvVSjtbo%3D E. K. Anderberg, T. Lindmark, and P. Artursson. Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route. Pharm. Res. 10:857–864 (1993).
20. 20. J. D. Soderholm H. Oman L. Blomquist J. Veen T. Lindmark G. Olaison 1998 Reversible increase in tight junction permeability to macromolecules in rat ileal mucosa in vitro by sodium caprate, a constituent of milk fat Dig. Dis. Sci. 43 1547 1552 9690393 10.1023/A:1018823100761 1:CAS:528:DyaK1cXltlCht70%3D J. D. Soderholm, H. Oman, L. Blomquist, J. Veen, T. Lindmark, and G. Olaison. Reversible increase in tight junction permeability to macromolecules in rat ileal mucosa in vitro by sodium caprate, a constituent of milk fat. Dig. Dis. Sci. 43:1547–1552 (1998).
21. 21. M. Tomita M. Hayashi T. Horie T. Ishizawa S. Awazu 1988 Enhancement of colonic drug absorption by the transcellular permeation route Pharm. Res. 5 786 789 3247289 10.1023/A:1015992819290 1:CAS:528:DyaL1MXhtVWlsLY%3D M. Tomita, M. Hayashi, T. Horie, T. Ishizawa, and S. Awazu. Enhancement of colonic drug absorption by the transcellular permeation route. Pharm. Res. 5:786–789 (1988).
22. 22. P. Sharma M. V. S. Varma H. P. S. Chawla R. Panchagnula 2005 In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies Il Farmaco 60 874 883 16243320 10.1016/j.farmac.2005.08.007 1:CAS:528:DC%2BD2MXhtFyktrjP P. Sharma, M. V. S. Varma, H. P. S. Chawla, and R. Panchagnula. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Il Farmaco. 60:874–883 (2005).
23. 23. M. Sakai T. Imai H. Ohtake H. Azuma M. Otagiri 1997 Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers: Assessment by confocal laser scanning microscopy J. Pharm. Sci. 86 779 785 9232516 10.1021/js960529n 1:CAS:528:DyaK2sXjslCkt78%3D M. Sakai, T. Imai, H. Ohtake, H. Azuma, and M. Otagiri. Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers: Assessment by confocal laser scanning microscopy. J. Pharm. Sci. 86:779–785 (1997).
24. 24. M. Tomita M. Hayashi S. Awazu 1996 Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells J. Pharm. Sci. 85 608 611 8773957 10.1021/js9504604 1:CAS:528:DyaK28XivVCnsr8%3D M. Tomita, M. Hayashi, and S. Awazu. Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells. J. Pharm. Sci. 85:608–611 (1996).
25. 25. E. Fuller C. Duckham E. Wood 2007 Disruption of epithelial tight junctions by yeast enhances the paracellular delivery of a model protein Pharm. Res. 24 37 47 16969693 10.1007/s11095-006-9124-0 1:CAS:528:DC%2BD28Xht1yis7zI E. Fuller, C. Duckham, and E. Wood. Disruption of epithelial tight junctions by yeast enhances the paracellular delivery of a model protein. Pharm. Res. 24:37–47 (2007).
26. 26. K. Whitehead, N. Karr, and S. Mitragotri. Safe and effective enhancers for oral drug delivery. Pharm Res. in press. DOI 10.1007/s11095-007-9488-9.
27. 27. N. A. Motlekar K. S. Srivenugopal M. S. Wachtel B.-B. C. Youan 2005 Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels J. Drug Target 13 573 583 16390818 10.1080/10611860500471906 1:CAS:528:DC%2BD2MXhtlGht7zM N. A. Motlekar, K. S. Srivenugopal, M. S. Wachtel, and B.-B. C. Youan. Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels. J. Drug Target 13:573–583 (2005).
28. 28. B. Aspenstrom-Fagerlund L. Ring P. Aspenstrom J. Tallkvist N.-G. Ilback A. W. Glynn 2007 Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes Toxicology 237 12 23 17560003 10.1016/j.tox.2007.04.014 B. Aspenstrom-Fagerlund, L. Ring, P. Aspenstrom, J. Tallkvist, N.-G. Ilback, and A. W. Glynn. Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes. Toxicology 237:12–23 (2007).
29. 29. G. Fotakis J. A. Timbrell 2006 in vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride Toxicol. Let. 160 171 177 10.1016/j.toxlet.2005.07.001 1:CAS:528:DC%2BD2MXhtFOhtbnE G. Fotakis, and J. A. Timbrell. in vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol. Let. 160:171–177 (2006).
30. 30. E. S. Swenson W. Curatolo 1992 Intestinal permeability enhancement for proteins, peptides, and other polar drugs: Mechanisms and potential toxicity Adv. Drug Deliv. Rev. 8 39 92 10.1016/0169-409X(92)90015-I 1:CAS:528:DyaK38XptFWqsg%3D%3D E. S. Swenson, and W. Curatolo. Intestinal permeability enhancement for proteins, peptides, and other polar drugs: Mechanisms and potential toxicity. Adv. Drug Deliv. Rev. 8:39–92 (1992).
31. 31. W. P. Soutter P. Sasieni T. Panoskaltsis 2006 Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia Int. J. Cancer 118 2048 2055 16284947 10.1002/ijc.21604 1:CAS:528:DC%2BD28Xjt1Gqu7o%3D W. P. Soutter, P. Sasieni, and T. Panoskaltsis. Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia. Int. J. Cancer 118:2048–2055 (2006).
32. 32. C. Pilette, B. Colinet, R. Kiss, S. Andre, H. Kaltner, H. J. Gabius, M. Delos, J. P. Vaerman, M. Decramer, and Y. Sibille. Increased galectin-3 expression and intraepithelial neutrophils in small airways in severe chronic obstructive pulmonary disease. Eur. Respir. J. 29:914-922 (2007). DOI 09031936.00073005.
33. 33. K. Ishida M. Takaai Y. Hashimoto 2006 Pharmacokinetic analysis of transcellular transport of quinidine across monolayers of human intestinal epithelial Caco-2 cells Biol. Pharm. Bull. 29 522 526 16508158 10.1248/bpb.29.522 1:CAS:528:DC%2BD28XjslyrtbY%3D K. Ishida, M. Takaai, and Y. Hashimoto. Pharmacokinetic analysis of transcellular transport of quinidine across monolayers of human intestinal epithelial Caco-2 cells. Biol. Pharm. Bull. 29:522–526 (2006).
34. 34. A. Fasano J. P. Nataro 2004 Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins Adv. Drug Deliv. Rev. 56 795 807 15063590 10.1016/j.addr.2003.10.045 1:CAS:528:DC%2BD2cXivVGit7w%3D A. Fasano, and J. P. Nataro. Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins. Adv. Drug Deliv. Rev. 56:795–807 (2004).
35. 35. T. Lindmark T. Nikkila P. Artursson 1998 Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells J. Pharmacol. Exp. Ther. 284 362 369 9435199 1:CAS:528:DyaK1cXltlCqsA%3D%3D T. Lindmark, T. Nikkila, and P. Artursson. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J. Pharmacol. Exp. Ther. 284:362–369 (1998).
36. 36. A. Marin H. Sun G. A. Husseini W. G. Pitt D. A. Christensen N. Y. Rapoport 2002 Drug delivery in pluronic micelles: Effect of high-frequency ultrasound on drug release from micelles and intracellular uptake J. Control. Rel. 84 39 47 10.1016/S0168-3659(02)00262-6 1:CAS:528:DC%2BD38XnvFOnsrg%3D A. Marin, H. Sun, G. A. Husseini, W. G. Pitt, D. A. Christensen, and N. Y. Rapoport. Drug delivery in pluronic micelles: Effect of high-frequency ultrasound on drug release from micelles and intracellular uptake. J. Control. Rel. 84:39–47 (2002).
37. 37. D. M. Hallow A. D. Mahajan M. R. Prausnitz 2007 Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries J. Control. Rel. 118 285 293 10.1016/j.jconrel.2006.12.029 1:CAS:528:DC%2BD2sXjtlyrsbc%3D D. M. Hallow, A. D. Mahajan, and M. R. Prausnitz. Ultrasonically targeted delivery into endothelial and smooth muscle cells in ex vivo arteries. J. Control. Rel. 118:285–293 (2007).
38. 38. E. B. Ghartey-Tagoe J. S. Morgan K. Ahmed A. S. Neish M. R. Prausnitz 2004 Electroporation-mediated delivery of molecules to model intestinal epithelia Int. J. Pharm. Sci. 270 127 138 10.1016/j.ijpharm.2003.10.009 1:CAS:528:DC%2BD2cXit1Cmsw%3D%3D E. B. Ghartey-Tagoe, J. S. Morgan, K. Ahmed, A. S. Neish, and M. R. Prausnitz. Electroporation-mediated delivery of molecules to model intestinal epithelia. Int. J. Pharm. Sci. 270:127–138 (2004).