Acyloxyalkoxy-based cyclic prodrugs of opioid peptides: Evaluation of the chemical and enzymatic stability as well as their transport properties across Caco-2 cell monolayers

Pharmaceutical Research

Volumn 16, Issue 1, 1999, Pages 24-29

  Bak, Annette ^a   Gudmundsson, Olafur S ^b,c   Friis, Gitte J ^a   Siahaan, Teruna J ^b   Borchardt, Ronald T ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF KANSAS   (United States)

^c BRISTOL MYERS SQUIBB PHARMACEUTICAL RESEARCH INSTITUTE   (United States)

Author keywords

Caco 2 cells; Chemical and enzymatic stability of peptides; Esterase sensitive prodrugs; Opioid peptides; Peptide deliyery

Indexed keywords

ENKEPHALIN[2 DEXTRO ALANINE 5 DEXTRO LEUCINE]; LEUCINE ENKEPHALIN; OPIATE PEPTIDE; PRODRUG;

ARTICLE; CATALYSIS; CELL MEMBRANE PERMEABILITY; CELL TRANSPORT; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME STABILITY; HUMAN; HUMAN CELL; LIPOPHILICITY; LIVER HOMOGENATE; MONOLAYER CULTURE; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; STOICHIOMETRY;

ACYLATION; ALKYLATION; ANIMALS; BIOLOGICAL TRANSPORT; CACO-2 CELLS; CHEMISTRY, PHYSICAL; ENZYME STABILITY; EVALUATION STUDIES; HUMANS; LINEAR MODELS; PEPTIDES, CYCLIC; PRODRUGS; RATS;

EID: 0032908281     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1018854308829     Document Type: Article

References (19)

1. B. Wang, K. Nimkar, W. Wang, H. Zhong, D. Shen, O. S. Gudmundsson, S. Gangwar, T. J. Siahaan, and R. T. Borchardt. Synthesis and evaluation of the physicochemical properties of esterase-sensitive cyclic prodrugs of opioid peptides using phenylpropionic acid and coumarinic acid linkers. J. Peptide Res. (in press).
2. O. S. Gudmundsson, G. M. Pauletti, W. Wang, D. Shan, H. Zhang, B. Wang, and R. T. Borchardt. Coumarinic acid-based cyclic prodrugs of opioid peptides that exhibit metabolic stability to peptidases and excellent cellular permeability. Pharm. Res. 16:7-15 (1999).
3. O. S. Gudmundsson, K. Nimkar, S. Gangwar, T. J. Siahaan, and R. T. Borchardt. Phenylpropionic acid-based cyclic prodrugs of opioid peptides that exhibit metabolic stability to peptidases and excellent cellular permeability, Pharm. Res. 16:16-23 (1999).
4. S. Gangwar, G. M. Pauletti, T. J. Siahaan, V. J. Stella, and R. T. Borchardt. Synthesis of a novel esterase-sensitive cyclic prodrug of a hexapeptide using an acyloxyalkoxy promoiety. J. Org. Chem. 62:1356-1362 (1997).
5. G. M. Pauletti, S. Gangwar, F. W. Okumu, T. J. Siahaan, V. J. Stella, and R. T. Borchardt. Esterase-sensitive cyclic prodrugs of peptides: evaluation of an acyloxyalkoxy promoiety in a model hexapeptide. Pharm. Res. 13:1615-1623 (1996).
6. S. Gangwar, S. D. S. Jois, T. J. Siahaan, D. G. Vander Velde, V. J. Stella, and R. T. Borchardt. The effect of conformation on membrane permeability of an acyloxyalkoxy-linked cyclic prodrug of a model peptide. Pharm. Res. 13:1657-1661 (1996).
7. A. Bak, T. J. Siahaan, O. J. Gudmundsson, S. Gangwar, G. J. Friis, and R. T. Borchardt. Synthesis and evaluation of the physicochemical properties of esterase-sensitive cyclic prodrugs of opioid peptides using an (acyloxy)alkoxy linker. J. Peptide Res. (in press).
8. I. J. Hidalgo, T. J. Raub, and R. T. Borchardt. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736-740 (1989).
9. J. Hughes, Centrally acting peptides; University Park Press, Baltimore, MD, 1977.
10. J. M. Hambrook, B. A. Morgan, M. J. Rance, and C. F. C. Smith. Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262:782-783 (1976).
11. R. Oliyai. Prodrugs of peptides and peptidomimetics for improved formulation and delivery. Adv. Drug Del. Rev. 19:275-286 (1996).
12. H. Bundgaard. Means to enhance penetration. Prodrugs as a means to improve the delivery of peptide drugs. Adv. Drug Del. Rev. 8:1-38 (1992).
13. S. Gangwar. G. M. Pauletti, B. Wang, T. J. Siahaan, V. J. Stella, and R. T. Borchardt. Prodrug strategies to enhance the intestinal absorption of peptides. Drug Discovery Today 2:148-155 (1997).
14. C. H. Walker and M. I. Mackness. "A" esterases and their role in regulating the toxicity of organophosphates. Arch. Toxicol. 60:30-33 (1987).
15. T. L. Huang, T. Shiotsuki, T. Uematsu, B. Borhan, Q. X. Li, and B. D. Hammock. Structure-activity relationships for substrates and inhibitors of mammalian liver microsomal carboxylesterases. Pharm. Res. 13:1495-1499 (1996).
16. K. Takahashi, S. Tamagawa, H. Sakano, T. Katagi, and N. Mizuno. Effects on the ester moiety on stereoselective hydrolysis of several propranolol prodrugs in rat tissue. Biol. Pharm. Bull. 18:1401-1404 (1995).
17. P. S. Burton, J. T. Goodwin, R. A. Conradi, N. F. H. Ho, and A. R. Hilgers. In vitro permeability of peptidomimetic drugs: The role of polarized efflux pathways as additional barriers to absorption. Adv. Drug Del. Rev. 23:143-156 (1997).
18. O. S. Gudmundsson, S. D. S. Jois, D. G. Vander Velde, T. J. Siahaan, B. Wang, and R. T. Borchardt. The effect of conformation on the membrane permeability of coumarinic acid- and phenylpropionic acid-based cyclic prodrugs of opioid peptides. J. Peptide Res. (in press).
19. O. S. Gudmundsson, D. G. Vander Velde, S. D. S. Jois, A. Bak, T. J. Siahaan, and R. T. Borchardt. The effect of conformation on the membrane permeability of acyloxyalkoxy-based cyclic prodrugs of opioid peptides. J. Peptide Res. (in press)