Delivery agents that facilitate the absorption of macromolecular drugs

Current Opinion in Drug Discovery and Development

Volumn 2, Issue 1, 1999, Pages 26-32

  Leone Bay, Andrea ^a   Paton, Duncan R ^a  

^a Emisphere Technologies Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; ANTIBODY; BACITRACIN; BLOOD CLOTTING FACTOR 10A INHIBITOR; CHYMOSTATIN; DESMOPRESSIN; DEXTRAN DERIVATIVE; EDETIC ACID; ENZYME INHIBITOR; GAMMA INTERFERON; HEPARIN; HUMAN GROWTH HORMONE; LEUPRORELIN; LIPOSOME; NIOSOME; OCTANOIC ACID DERIVATIVE; OLEIC ACID; PEPSTATIN DERIVATIVE; PHOSPHOLIPID; POLIDOCANOL; PRODRUG; SALCATONIN; SORBITAN; TRANSMEMBRANE CONDUCTANCE REGULATOR; VASOPRESSIN; WARFARIN;

CLINICAL TRIAL; DOSE RESPONSE; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG HALF LIFE; HUMAN; INTRANASAL DRUG ADMINISTRATION; LIPOPHILICITY; MUCOSA; NONHUMAN; ORAL DRUG ADMINISTRATION; PARTIAL THROMBOPLASTIN TIME; PHYSICAL CHEMISTRY; REVIEW; SUBCUTANEOUS DRUG ADMINISTRATION; TRANSDERMAL DRUG ADMINISTRATION;

EID: 0032960266     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (90)

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30. A well-written and extensive review that discusses mucosal physiology, fundamental transmucosal delivery and recent progress in systemic delivery of therapeutic proteins across various mucosae. The transmucosal delivery of enkephalin, catcitonin and insulin are presented as case studies.
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36. Penetration enhancers were used to increase the bioavailability of leuprolide in both rats and humans. Relative bioavailability in man was 2.4% (nasally) and 28% (pulmonary).
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38. Nasal Interferon absorption was enhanced by the use of sodium glycholate, ethylenediaminetetraacetic acid, sodium caprytate and sodium salicylate. Sodium glycholate is the most effective delivery agent and acts as both a penetration enhancer and an enzyme inhibitor.
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40. The nasal delivery of vasopressin facilitated by hyaluronate sodium was directly related to the dose of hyaluronate.
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43. The nasal absorption of CTFR protein was demonstrated in mice using phospholipid liposomes as the delivery agent.
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45. The nasal bioavailability of human growth hormone using L-alphalysophosphatidylcholine was 16% in rats, 73% in rabbits and 16% in sheep.
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51. Various protease inhibitors and penetration enhancers were evaluated for their effectiveness in promoting the pulmonary absorption of salmon calcitonin. Co-administration of salmon calcitonin with bacitracin and chymostatin elicited the highest systemic drug levels.
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53. Bioavailabilities as high as 40% were obtained following administration of leuprolide in combination with ethanol in beagle dogs.
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55. Pulmonary delivery of leuprolide could be enhanced by sorbitan and oleates. Bioavailabilities of 4 to 18% were obtained.
56. Smith PL, Wall DA, Gochoco CH, Wilson G: Routes of delivery: case studies. Oral absorption of peptides and proteins. Adv Drug Deliv Rev (1992) 8:253-290.
57. An excellent review of examples of peptide and protein drugs for which oral bioavailability in man has been well documented. A critique of strategies under investigation to improve the oral absorption of a wide range of peptide and protein molecules is also included.
58. Wang W: Oral protein drug delivery. J Drug Target (1996) 4:195-232.
59. This review presents a discussion of oral protein drug delivery with emphasis on the gastrointestinal barriers to oral protein delivery, protein absorption mechanisms in the gastrointestinal tract and various oral protein delivery strategies.
60. Fix JA: Oral controlled release technology for peptides: status and future prospects. Pharm Res (1996) 13:17601764.
61. A discussion of the problems associated with oral peptide delivery including poor permeability, enzymatic degradation, rapid clearance and confonnational instability.
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63. This review focuses on the regional differences within the intestine in enzymatic activity, permeability and absorption, and in the response of these regions to absorption enhancers for the delivery of peptides and proteins. Delivery systems for site-specific delivery are also described.
64. Bemkop-Schnurch A: The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins. JCont Re/(1998) 52:1-16. The current status of using enzyme inhibitors as oral drug delivery agents is reviewed. The inhibitors included are non-amino acid based inhibitors, modified amino acid inhibitors and polypeptide protease inhibitors.
65. Fix JA: Strategies for delivery of peptides utilizing absorption-enhancing agents. J Pharm Sei (1996) 85:12821285.
66. This report reviews the literature and current data. The author concludes that successful oral peptide delivery will most likely be determined by the balance between absorption-promoting efficacy and the extent to which transient alteration of cell or tissue morphology occurs.
67. Bemkop-Schnurch A, Schwarz GH, Kratzel M: Modified mucoadhesive polymers for the peroral administration of mainly elastase degradable therapeutic (poly)peptides. J Conl Pel (1997) 47:113-121.
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71. Enzyme inhibitors are covalently bound to nonabsorbable polymers and evaluated for their enzyme inhibitory activities and potential use in an oral drug delivery system.
72. Leone-Bay A, Ho KK, Agarwal R, Baughman RA, Chaudhary K, DeMorin F, Genoble L, Mclnnes C, Lercara C, Milstein S, OToole D, Sarubbi D, Variano B, Paton DR: 4-[4-(2hydroxybenzoyl)aminophenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone. J Med Chem (1996) 39:2571-2578.
73. Seventy compounds were evaluated for their ability to facilitate the oral absorption of recombinant human growth hormone (rhGH) in rats. Of these, one delivery agent was identified as a preclinical candidate and was used to demonstrate the successful oral delivery of rhGH in monkeys.
74. Leone-Bay A, Palon DR, Freeman J, Lercara C, OToole D, Gschneidner D, Wang E, Harris E, Rosado C, Rivera T, De Vincent A, Tai M, Mercogliano F, Agarwal R, Leipold H, Baughman RA: Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin. J Med Chem (1998) 41:1163-1171.
75. Sixty-eight compounds were evaluated for their ability to facilitate the oral absorption of heparin in rats. Of these, one delivery agent was identified as a preclinical candidate and was used to demonstrate the successful oral delivery of heparin in monkeys. The effectiveness of the delivery agents was correlated to their rate of travel through an immobilized artificial membrane chromatography column.
76. Leone-Bay A, Leipold H, Paton DR, Milstein SJ, Baughman RA: Oral delivery of rhGH: preliminary mechanistic considerations. Drug News Perspec/(1996) 9:586-590. Differential scanning calorimetry, capillary zone electrophoresis and molecular modelling were used to show that an interaction between the delivery agents and the protein drug is important for the oral absorption of rhGH.
77. Baughman RA, Kapoor SC, Agarwal RK, Kisicki J, CatellaLawsen F, FitzGerald GA: Oral delivery of anticoagulant doses of heparin. A randomized, double-blind, controlled study in humans. Circulation (1998) 98:1610-1615.
78. Oral administration of heparin in combination with the delivery agent SNAC, produces significant elevations in four indexes of anticoagulation effect in healthy, human volunteers.
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84. Brayden D, Creed E, O'Connell A, Leipold H, Agarwal R, Leone-Bay A: Heparin absorption across the intestine: effects of sodium /V-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers. Pharm Res (1997) 14:1772-1779.
85. In rat in situ models, SNAC enhanced heparin absorption without causing toxicity. The mechanism of permeation was evaluated in the Caco-2 cells.
86. Leone-Bay A, Paton DR, Variano B, Leipold H, Rivera T, Miura-Fraboni J, Baughman RA, Santiago N: Acylated non-aamino acids as novel agents for the oral delivery of heparin sodium, USP. J Cont Rel (1998) 50:41 -49. Ten acylated non-a-amino acids were usecJ to demonstrate the oral delivery of heparin in rats and primates. In vitro studies suggest that the gastrointestinal absorption of heparin is the result of a noncovalent interaction between heparin and the delivery agent.
87. Leone-Bay A, Leipold H, Agarwal R, Rivera T, Baughman RA: The evolution of an oral heparin dosing solution. Drugs Future (1997) 22:885-891.
88. A chronological review of the work leading to the development of an oral heparin dosing solution that facilitates the gastrointestinal absorption of heparin in rats, monkeys and healthy human subjects.
89. Rivera T, Leone-Bay A, Paton D, Leipold H, Baughman RA: Oral delivery of heparin in combination with sodium N-[8(2-hydroxybenzoyl)amino]caprylate: pharmacological considerations. Pharm Res (1997) 14:1830-1833.
90. Preclinical studies toward the development of an oral heparin formulation are reported including efficacy, toxicity, pharmacokinetics and histology.