← Back to Search
Emerging Trends In Oral Delivery Of Peptide And Protein Drugs.
R. Mahato, A. Narang, L. Thoma, D. Miller
Published 2003 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Most peptide and protein drugs are currently used as parenteral formulations because of their poor oral bioavailability. Development of an effective oral delivery system for these macromolecular drugs requires a thorough understanding of their physicochemical properties, such as molecular weight, hydrophobicity, ionization constants, and pH stability, as well as biological barriers that restrict protein and peptide absorption from the gastrointestinal (GI) tract, including pH variability, enzymatic degradation, and membrane efflux. Various strategies currently under investigation include amino acid backbone modifications, formulation approaches, chemical conjugation of hydrophobic or targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and absorption enhancers. However, there is only limited success because of the hostile environment of the GI tract--e.g., strong pH extremes and abundant presence of potent luminal enzymes. This review focuses on the challenges posed by the GI system and how different pharmaceutical approaches can be used to make oral delivery of protein and peptide drugs more feasible. The roles of P-glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and metabolism will also be discussed.
This paper references
Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers.
V. Lang (1997)
In‐vitro release and oral bioactivity of insulin in diabetic rats using nanocapsules dispersed in biocompatible microemulsion
Suchat Watnasirichaikul (2002)
The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins.
A. Bernkop-Schnürch (1998)
Transport of human growth hormone across Caco-2 cells with novel delivery agents: evidence for P-glycoprotein involvement.
S. J. Wu (1999)
Pharmacokinetic Considerations of New Insulin Formulations and Routes of Administration
A. Hoffman (1997)
In vitro degradation of pH-sensitive hydrogels containing aromatic azo bonds.
H. Ghandehari (1997)
Epithelial cell specialization within human Peyer's patches: an ultrastructural study of intestinal lymphoid follicles.
R. L. Owen (1974)
Oral Delivery of Biologically Active Parathyroid Hormone
A. Leone-Bay (2004)
Intestinal transmission of macromolecules (BSA and FITC-labelled dextrans) in the neonatal pig. Influence of age of piglet and molecular weight of markers.
B. Weström (1984)
Determinants of reovirus interaction with the intestinal M cells and absorptive cells of murine intestine.
J. L. Wolf (1983)
Biochemistry of multidrug resistance mediated by the multidrug transporter.
M. Gottesman (1993)
Oral immunization with a synthetic peptide of cholera toxin B subunit. Obtention of neutralizing antibodies.
A. Guyon-Gruaz (1986)
The transport of vitamin B12 through polarized monolayers of Caco-2 cells.
C. Dix (1990)
Developments in the area of bioadhesive drug delivery systems
C. Lehr (2002)
Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation.
E. Butcher (1982)
Incorporation of the reovirus M cell attachment protein into small unilamellar vesicles: incorporation efficiency and binding capability to L929 cells in vitro.
W. Rubas (1990)
Gastrointestinal absorption of drugs: methods and studies
L. Barthe (1999)
Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.
V. Chadwick (1977)
pH-induced solubility transition of sulfonamide-based polymers.
S. I. Kang (2002)
Prediction of Membrane Permeability to Peptides from Calculated Dynamic Molecular Surface Properties
P. Stenberg (2004)
Structural changes in the arginine vasopressin molecule that prolong its antidiuretic action.
W. H. Sawyer (1974)
Binding and transepithelial transport of immunoglobulins by intestinal M cells: demonstration using monoclonal IgA antibodies against enteric viral proteins
R. Weltzin (1989)
The effect of food and cholestyramine on the absorption of cyclosporine in cardiac transplant recipients.
A. Keogh (1988)
Biorecognition of HPMA copolymer-lectin conjugates as an indicator of differentiation of cell-surface glycoproteins in development, maturation, and diseases of human and rodent gastrointestinal tissues.
S. Wróblewski (2000)
Humoral regulation of vitamin B12 absorption by pregnant mouse small intestine.
J. Brown (1977)
Oral insulin product hexyl-insulin monoconjugate 2 (HIM2) in type 1 diabetes mellitus: the glucose stabilization effects of HIM2.
S. Clement (2002)
Enhanced Oral Uptake of Tomato Lectin-Conjugated Nanoparticles in the Rat
N. Hussain (2004)
The gut‐associated lymphoid system: nature and properties of the large dividing cells
D. Guy‐Grand (1974)
Design of nanoparticles composed of graft copolymers for oral peptide delivery.
S. Sakuma (2001)
Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals
T. Kararli (1995)
Stabilization of Glycoenzymes by Cross‐linking of Their Carbohydrate Chains
S. Barbarić (1988)
Role of the interstitial matrix during intestinal volume absorption.
D. Granger (1980)
Murine Peyer's patch T cell clones. Characterization of antigen- specific helper T cells for immunoglobulin A responses
H. Kiyono (1982)
Barrier function of epithelia.
D. Powell (1981)
Peroral route: an opportunity for protein and peptide drug delivery.
A. Sood (2001)
Specific adherence of Escherichia coli (strain RDEC-1) to membranous (M) cells of the Peyer's patch in Escherichia coli diarrhea in the rabbit.
L. Inman (1983)
pH-sensitive polymers that enhance intracellular drug delivery in vivo.
T. Kyriakides (2002)
Structure, distribution, and origin of M cells in Peyer's patches of mouse ileum.
W. A. Bye (1984)
An oral preparation to release drugs in the human colon.
M. Dew (1982)
The Effects of Enprostil and RS‐86505‐007 on In‐vitro Intestinal Permeability of Rabbit and Monkey
G. Grass (1990)
Improvement of Intestinal Absorption of Thyrotropin‐releasing Hormone by Chemical Modification with Lauric Acid
K. Yamada (1992)
Effects of Various Protease Inhibitors on the Intestinal Absorption and Degradation of Insulin in Rats
A. Yamamoto (2004)
Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosan-EDTA conjugates.
A. Bernkop-Schnürch (1998)
Acylation of Human Insulin With Palmitic Acid Extends the Time Action of Human Insulin in Diabetic Dogs
S. Myers (1997)
Absorption of cyclosporine from rabbit small intestine in situ.
R. Sawchuk (1986)
The effect of additives on the oral mucosal absorption of human calcitonin in rats.
Y. Nakada (1988)
Morphometric and cytochemical analysis of lysosomes in rat Peyer's patch follicle epithelium: Their reduction in volume fraction and acid phosphatase content in M cells compared to adjacent enterocytes
R. L. Owen (1986)
Five types of lymphocytes (lg− θ−, lg− θ+ weak, lg− θ+strong, lg+ θ− and lg+ θ+) characterized by double immunofluorescence and electrophoretic mobility Organ distribution in normal and nude mice
G. E. Roelants (1975)
Restrictive Transport of a Lipid‐Soluble Peptide (Cyclosporin) Through the Blood–Brain Barrier
W. Cefalu (1985)
Mononuclear phagocyte system of human Peyer's patches: an immunohistochemical study using monoclonal antibodies.
Y. Mahida (1989)
Intestinal peptide hydrolases differences between brush border and cytoplasmic enzymes.
W. Heizer (1972)
Biology and pathology of the intestinal M-cell. A review.
H. Egberts (1985)
Structural Specificity of Mucosal-Cell Transport and Metabolism of Peptide Drugs: Implication for Oral Peptide Drug Delivery
J. P. Bai (2004)
Regulation of Intercellular Tight Junctions by Zonula Occludens Toxin and Its Eukaryotic Analogue Zonulin
A. Fasano (2000)
Nasal delivery of polypeptides I: nasal absorption of enkephalins in rats.
K. S. Su (1985)
Canine Peyer's patches: macroscopic, light microscopic, scanning electron microscopic and immunohistochemical investigations.
H. HogenEsch (1987)
Intestinal macromolecular transmission in the young rat: influence of protease inhibitors during development.
E. Telemo (1987)
Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats.
S. Caliph (2000)
Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro.
A. Fasano (1995)
Peptide hydrolases in the brush border and soluble fractions of small intestinal mucosa of rat and man
Y. S. Kim (1972)
Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat
J. Pappenheimer (2005)
Intestinal absorption of stereoisomers of dipeptides in the rat.
A. Asatoor (1973)
Potent central nervous system action of p-Glu-His-(3,3′-dimethyl)-Pro NH2, a stabilized analog of TRH, to stimulate gastric secretion in rats
Y. Taché (1984)
Transport of membrane-bound macromolecules by M cells in follicle-associated epithelium of rabbit Peyer's patch
M. Neutra (2004)
Liposomes as oral adjuvants.
S. Michalek (1989)
Oral Absorption of Peptides Through the Cobalamin (Vitamin B12) Pathway in the Rat Intestine
J. Alsenz (2004)
Paracellular intestinal absorption of glucose, creatinine, and mannitol in normal animals: relation to body size.
J. Pappenheimer (1990)
4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone.
A. Leone-Bay (1996)
Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P‐glycoprotein: Implications for drug delivery and activity in cancer chemotherapy
V. Wacher (1995)
Synthesis of Palmitoyl Derivatives of Insulin and Their Biological Activities
M. Hashimoto (2004)
Promoting effect of the new chymotrypsin inhibitor FK‐448 on the intestinal absorption of insulin in rats and dogs
S. Fujii (1985)
A Correlation Between the Permeability Characteristics of a Series of Peptides Using an in Vitro Cell Culture Model (Caco-2) and Those Using an in Situ Perfused Rat Ileum Model of the Intestinal Mucosa
Dong-Chool Kirn (2004)
The membranous epithelial (M) cell and the mucosal immune system.
J. L. Wolf (1984)
Influence of the route of administration on thyrotropin-releasing hormone concentration in the mouse brain
T. Mitsuma (2005)
Differentiated B lymphocytes. Potential to express particular antibody variable and constant regions depends on site of lymphoid tissue and antigen load
P. Gearhart (1979)
Biodegradable azopolymer coating for oral delivery of peptide drugs.
M. Saffran (1990)
Enhanced Intestinal Absorption of Cyclosporine in Rats Through the Reduction of Emulsion Droplet Size
B. Tarr (2004)
Selective biopsy of human Peyer's patches during ileal endoscopy.
T. Macdonald (1987)
Challenges for the oral delivery of macromolecules
M. Goldberg (2003)
Development of an azopolymer based colonic release capsule for delivering proteins/macromolecules.
C. L. Cheng (1994)
Effects of net transmucosal volume flux on lymph flow in the canine colon. Structural-functional relationship.
P. Kvietys (1981)
The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions
D. Guy‐Grand (1978)
A preliminary study of the pharmacodynamics and pharmacokinetics of a novel enkephalin analogue [Tyr-D.Arg-Gly-Phe(4NO2)·Pro·NH2 (BW443C)] in healthy volunteers
J. Posner (2004)
Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer's patch M cells.
R. L. Owen (1983)
THE EFFECT OF DIMETHYL SULFOXIDE ON THE ABSORPTION OF CYCLOSPORINE IN RATS
L. Elzinga (1989)
EFFECT OF NEW CHYMOTRYPSIN INHIBITOR (FK-448) ON INTESTINAL ABSORPTION OF INSULIN
M. Shinomiya (1985)
Molecular cloning and sequencing of the reovirus (serotype 3) S1 gene which encodes the viral ceil attachment protein σ1
L. Nagata (1984)
Sequence of reovirus haemagglutinin predicts a coiled-coil structure
R. Bassel-Duby (1985)
MANAGEMENT OF CRANIAL DIABETES INSIPIDUS WITH ORAL DESMOPRESSIN (DDAVP)
D. Cunnah (1986)
"M" cell distribution in follicle-associated epithelium of mouse Peyer's patch.
M. W. Smith (1980)
In vitro and in vivo drug interactions involving human CYP3A.
K. Thummel (1998)
A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity
D. Roemer (1977)
The turnover of the epithelium of the small intestine.
B. Creamer (1967)
Gastrointestinal dynamics and pharmacology for the optimum design of controlled-release oral dosage forms.
N. Read (1988)
Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833.
J. van Asperen (1997)
Desolvation Energy: A Major Determinant of Absorption, But Not Clearance, of Peptides in Rats
Michael S. Karls (2004)
Hybrid insulin cocrystals for controlled release delivery
M. Brader (2002)
Common Principles of Protein Translocation Across Membranes
G. Schatz (1996)
The effect of enzyme inhibitor and absorption site following [D‐ala2, D‐leu5]enkephalin oral administration in rats
H. J. Lee (2002)
Anzahl und Lokalisation der Peyerschen Platten im Dünndarm des Kaninchens (Oryctolagus cuniculus)
W. Sackmann (1977)
Hydrogels for site-specific oral drug delivery: synthesis and characterization.
H. Brøndsted (1991)
The Development of Delivery Agents that Facilitate the Oral Absorption of Macromolecular Drugs
A. Leone-Bay (2000)
Novel Delivery Systems for Oral Vaccines
D. O'hagan (1994)
Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules
W. Charman (1986)
Particles and macrophages in murine Peyer's patches.
M. Lefevre (1985)
Antidiuretic action of 1-deamino-(8-D-arginine)-vasopressin in unanesthetized rats.
I. Vavra (1974)
Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes.
M. Kipnes (2003)
Synthesis of bioadhesive lectin-HPMA copolymer-cyclosporin conjugates.
Z. Lu (2000)
Degradation of Insulin and Calcitonin and Their Protection by Various Protease Inhibitors in Rat Caecal Contents: Implications in Peptide Delivery to the Colon
H. Tozaki (1997)
Enhancement of intestinal transport of thyrotropin-releasing hormone via a carrier-mediated transport system by chemical modification with lauric acid.
K. Tanaka (1996)
Protein σ1 is the reovirus cell attachment protein
P. Lee (1981)
Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.
V. Chadwick (1977)
Novel pH-sensitive hydrogels with adjustable swelling kinetics.
E. O. Akala (1998)
Drug delivery to the gastrointestinal tract
J. G. Hardy (1989)
Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction
M. Hebert (1992)
Comparison of gastrointestinal pH in dogs and humans: implications on the use of the beagle dog as a model for oral absorption in humans.
C. Y. Lui (1986)
In vitro intestinal transport of vasopressin and its analogues.
H. Vilhardt (1986)
Development of the Gastrointestinal Mucosal Barrier
J. Udall (1984)
Quantitative determination of macromolecular transport rate across intestinal Peyer's patches.
D. Keljo (1983)
Oral delivery of glucagon-like peptide-1 in a modified polymer preparation normalizes basal glycaemia in diabetic db/db mice
J. Joseph (2000)
Enhanced Permeability of Molecular Weight Markers and Poorly Bioavailable Compounds Across Caco-2 Cell Monolayers Using the Absorption Enhancer, Zonula Occludens Toxin
D. S. Cox (2004)
Role of P-Glycoprotein in Pharmacokinetics
J. Lin (2003)
Evidence for Site-Specific Absorption of a Novel ACE Inhibitor
G. Grass (2004)
Study on the peroral absorption of the endekapeptide cyclosporine A.
W. Ritschel (1989)
Enkephalin analogues containing β‐naphthylalanine at the fourth position
D. Mierke (1990)
In Vitro Measurement of Gastrointestinal Tissue Permeability Using a New Diffusion Cell
G. Grass (2004)
Antidiuretic effect of perorally administered DDAVP in hydrated humans.
H. Vilhardt (1984)
Utilizing Bile Acid Carrier Mechanisms to Enhance Liver and Small Intestine Absorption
N. F. Ho (1987)
The antidiuretic action of 1-deamino-8-D-arginine vasopressin (DDAVP) in man.
J. Radó (1976)
Oral Absorption of Peptides: The Effect of Absorption Site and Enzyme Inhibition on the Systemic Availability of Metkephamid
P. Langguth (2004)
Intestinal absorption mechanisms of thyrotropin-releasing hormone.
S. Yokohama (1984)
Enkephalin hydrolysis in homogenates of various absorptive mucosae of the albino rabbit: similarities in rates and involvement of aminopeptidases.
S. D. Kashi (1986)
Pinocytosis and phagocytosis: the effect of size of a particulate substrate on its mode of capture by rat peritoneal macrophages cultured in vitro.
M. Pratten (1986)
Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model.
A. Fasano (1997)
Screening for human ADME/Tox drug properties in drug discovery.
A. Li (2001)
On the dose dependency of Cyclosporin a absorption and disposition in healthy volunteers
J. Reymond (2005)
Effect of BW 942C, an enkephalinlike pentapeptide, on sodium and chloride transport in the rabbit ileum.
H. Berschneider (1988)
Comparative, quantitative study of lymphoid and non-lymphoid uptake of 60 nm polystyrene particles.
A. M. Hillery (1994)
Multifunctional matrices for oral peptide delivery.
A. Bernkop-Schnürch (2001)
Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells.
P. Artursson (1991)
Intestinal absorption and excretion of octapeptides composed of D amino acids.
J. Pappenheimer (1994)
A comparison of thyrotropin-releasing hormone with analogs: influence of disposition upon pharmacology.
M. Hichens (1983)
Human P-glycoprotein transports cyclosporin A and FK506.
T. Saeki (1993)
The metabolic barrier of the lower intestinal tract of salmon to the oral delivery of protein and peptide drugs.
R. Ledger (2002)
The proliferative response of cloned Peyer's patch switch T cells to syngeneic and allogeneic stimuli.
H. Kawanishi (1985)
Oral Controlled Release Technology for Peptides: Status and Future Prospects
J. Fix (2004)
CYP3A gene expression in human gut epithelium.
J. Kolars (1994)
Enhanced permeability of tetragastrin across the rat intestinal membrane and its reduced degradation by acylation with various fatty acids.
E. Yodoya (1994)
In vivo evidence that cobalamin is absorbed by receptor-mediated endocytosis in the mouse.
J. Robertson (1985)
Absorption of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in rabbits.
S. Lundin (1986)
A new approach to the oral administration of insulin and other peptide drugs.
M. Saffran (1986)
Intestinal M cells: a pathway for entry of reovirus into the host.
J. L. Wolf (1981)
Ionic Conductances of Extracellular Shunt Pathway in Rabbit Ileum
R. Frizzell (1972)
The absorption site of cyclosporin in the human gastrointestinal tract.
J. Drewe (1992)
Oral delivery of insulin using pH-responsive complexation gels.
A. Lowman (1999)
Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative analysis for contribution of enzymatic and transport barrier.
Y. Quan (1999)
Selective recognition of mucosal lymphoid high endothelium by gut intraepithelial leukocytes.
M. Schmitz (1988)
Effect of Size and Charge on the Passive Diffusion of Peptides Across Caco-2 Cell Monolayers via the Paracellular Pathway
G. Pauletti (2004)
Structural features of and cholesterol distribution in M-cell membranes in guinea pig, rat, and mouse Peyer's patches.
J. Madara (1984)
Surface and intracellular markers of mouse mesenteric and peripheral lymph node and Peyer's patch cells.
M. McWilliams (1974)
Relationships between mucosal hydrolysis and transport of two phenylalanine dipeptides.
D. Silk (1976)
Enteral absorption of octreotide: absorption enhancement by polyoxyethylene‐24‐cholesterol ether
J. Drewe (1993)
Preparation of Biodegradable Insulin Nanocapsules from Biocompatible Microemulsions
Suchat Watnasirichaikul (2004)
N-acylated alpha-amino acids as novel oral delivery agents for proteins.
A. Leone-Bay (1995)
Expression of cobalamin transport proteins and cobalamin transcytosis by colon adenocarcinoma cells.
K. Ramanujam (1991)
Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis.
J. S. Wassef (1989)
A mechanistic analysis of carrier-mediated oral delivery of protein therapeutics.
B. R. Stoll (2000)
Permeability and absorption of leuprolide from various intestinal regions in rabbits and rats.
Y. Zheng (1999)
Postnatal development of peptidase enzymes in rat small intestine.
G. Vaeth (1982)
Longitudinal study of the human intestinal brush border membrane proteins. Distribution of the main disaccharidases and peptidases.
N. Triadou (1983)
Porosity of the basement membrane overlying Peyer's patches in rats and monkeys.
S. McClugage (1986)
Number, size, and distribution of Peyer's patches in the human small intestine
J. S. Cornes (1965)
Intestinal permeability to polyethyleneglycol 600 in relation to macromolecular 'closure' in the neonatal pig.
B. Weström (1984)
Lipid-based formulations for intestinal lymphatic delivery.
C. O'Driscoll (2002)
Insulin and the gastrointestinal tract
M. Saffran (1997)
Regulation of the movement of solutes across tight junctions.
J. Madara (1998)
Poliovirus type 1 enters the human host through intestinal M cells.
P. Sicinski (1990)
Generation and characterization of monoclonal antibodies recognizing follicle epithelial M cells in rabbit gut-associated lymphoid tissues.
J. Pappo (1989)
Hydrogels for Site-Specific Drug Delivery to the Colon: In Vitro and in Vivo Degradation
H. Brøndsted (2004)
Ferritin: structure, biosynthesis, and role in iron metabolism.
H. Munro (1978)
The Mechanism of Uptake of Biodegradable Microparticles in Caco-2 Cells Is Size Dependent
M. P. Desai (2004)
Radiotelemetric determination of gastrointestinal pH in four healthy beagles.
C. A. Youngberg (1985)
Lymphocyte emigration from lymph nodes by blood in the pig and efferent lymph in the sheep.
R. Binns (1985)
The Oral Absorption of Micro- and Nanoparticulates: Neither Exceptional Nor Unusual
A. Florence (2004)
Small-bowel length and the dose of cyclosporine in children after liver transplantation.
P. Whitington (1990)
Rat Jejunal Permeability and Metabolism of μ-Selective Tetrapeptides in Gastrointestinal Fluids from Humans and Rats
E. Krondahl (2004)
PEG 400, a hydrophilic molecular probe for measuring intestinal permeability.
T. Ma (1990)
The site of absorption of cyclosporin A in the small intestine of the rat: a preliminary report.
Y. Ogino (1999)
Intestinal uptake and transmission of macromolecules into the blood in the young guinea pig.
Ekström Gm (1992)
Enzymatic barriers for GI peptide and protein delivery.
Woodley Jf (1994)
Pharmacokinetics of oral cyclosporin a (Sandimmun) in healthy subjects
J. Grevel (2004)
Retention of Ingested Latex Particles in Peyer's Patches of Germfree and Conventional Mice 1
M. Lefevre (1985)
Intestinal absorption mechanisms of γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417) and thyrotropin-releasing hormone (TRH)
S. Yokohama (1985)
D. J. White (2012)
Absorption of cyclosporine A after oral dosing.
J. Grevel (1986)
Degradation and Aggregation of Human Calcitonin In Vitro
R. Lu (2004)
Peyer's patches export lymphocytes throughout the lymphoid system in sheep.
R. Pabst (1987)
Tissue distribution, disposition, and metabolism of cyclosporine in rats.
O. Wagner (1987)
Effect of formulation adjuvants on gastrointestinal absorption of leuprolide acetate.
A. Adjei (1993)
Passive and Carrier-Mediated Intestinal Absorption Components of Two Angiotensin Converting Enzyme (ACE) Inhibitor Prodrugs in Rats: Enalapril and Fosinopril
D. I. Friedman (2004)
Microdissection by ultrasonication: porosity of the intestinal epithelial basal lamina.
S. McClugage (1984)
Evidence for a polarized efflux system in CACO-2 cells capable of modulating cyclosporin A transport.
P. Augustijns (1993)
Absorption of thyrotropin-releasing hormone after oral administration of TRH tartrate monohydrate in the rat, dog and human.
S. Yokohama (1984)
Distribution and biosynthesis of aminopeptidase N and dipeptidyl aminopeptidase IV in rat small intestine.
S. Miura (1983)
Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: absorption by various routes and absorption enhancement.
H. Okada (1982)
Peptide hydrolases of the human small intestinal mucosa: distribution of activities between brush border membranes and cytosol.
E. Sterchi (1980)
Regional variations in the composition of purified brush borders isolated from infant and adult rabbit small intestine.
G. Leitch (1971)
This paper is referenced by
Whey protein and alginate hydrogel microparticles for insulin intestinal absorption: evaluation of permeability enhancement properties on Caco-2 cells.
Emmanuelle Déat-Lainé (2013)
Current challenges in non-invasive insulin delivery systems: a comparative review.
E. Khafagy (2007)
EGFR-binding peptide: a patent evaluation of WO2014002836
Peng-Cheng Lv (2014)
The effect of multiple N-methylation on intestinal permeability of cyclic hexapeptides.
O. Ovadia (2011)
Improvement of enzymatic stability and intestinal permeability of deuterohemin-peptide conjugates by specific multi-site N-methylation
Qingguang Dong (2012)
Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome
I. Tessaro (2015)
Permeability of exendin-4-loaded chitosan nanoparticles across MDCK cell monolayers and rat small intestine.
M. Wang (2014)
Biodistribution of PLGA and PLGA/chitosan nanoparticles after repeat-dose oral delivery in F344 rats for 7 days.
S. M. Navarro (2014)
Oral Delivery of Proteins and Peptides: Concepts and Applications
Gaurang Patel (2011)
Physicochemical Characteristics of Molecules and Their Diffusion across Human Vaginal Mucosa
A.D. Van Eyk (2008)
EPITHELIAL CELL SURFACE TARGETING USING SYNTHETIC D-AMINO ACID PEPTIDES
T. Sroka (2006)
Peptides, proteins and antibodies
A. Lalatsa (2013)
Advanced Approaches of Bioactive Peptide Molecules and Protein Drug Delivery Systems.
N. Thotakura (2018)
Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration.
X. Zhang (2012)
Handbook of Preformulation: Chemical, Biological, and Botanical Drugs
S. Niazi (2006)
Characterization of water-in-oil microemulsion for oral delivery of earthworm fibrinolytic enzyme.
Mao-Bo Cheng (2008)
Patient friendly strategy via chemical modification of proteins and peptides in oral delivery
Beom-Jin Lee (2016)
Peptide-Mediated Nanoparticle Drug Delivery System
Saurabh Bhatia (2016)
Buccal transmucosal delivery of large molecule therapeutics using orally disintegrating tablet technology
Affiong Iyire (2016)
Impact of digestion on the transport of dextran-loaded self-emulsified nanoemulsion through MDCK epithelial cell monolayer and rat intestines.
Pulkit Khatri (2018)
Development of METx : a vasopressin agonist
S. Patel (2017)
Current Evidence on the Bioavailability of Food Bioactive Peptides
L. Amigo (2020)
Indole moiety induced biological potency in pseudo-peptides derived from 2-amino-2-(1H-indole-2-yl) based acetamides: Chemical synthesis, in vitro anticancer activity and theoretical studies
K. S. Prasad (2020)
Short peptides interfering with signaling pathways as new therapeutic tools for cancer treatment.
A. Ellert-Miklaszewska (2017)
An Investigation into the Use of a Plant-Expressed Virus-Like Particle as an Oral Vaccine Candidate
Alberto Berardi (2013)
Novel strategy to inhibit the oncogenic transcription factor c-Myc in triple-negative breast cancer
Rita Mejzini (2016)
Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus
K. Wang (2019)
COMPOSITION AND METHOD FOR MAKING OLIGO-BENZAMIDE COMPOUNDS
Optimization of mucoadhesive and mucopenetrant coatings for nanoformulations for oral delivery
Helena Isabel Teixeira de Sousa (2016)
Enhancing the therapeutic potential of peptide toxins
R. Norton (2017)
Insight of current technologies for oral delivery of proteins and peptides.
J. Chin (2012)
A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses.
A. E. Ibañez (2015)See more