Orally Administered Therapeutic Peptide Delivery: Enhanced Absorption Through the Small Intestine Using Permeation Enhancers

2012 ◽  
Vol 18 (3) ◽  
pp. 259-280 ◽  
Author(s):  
Viness Pillay ◽  
Angus R. Hibbins ◽  
Yahya E. Choonara ◽  
Lisa C. du Toit ◽  
Pradeep Kumar ◽  
...  
2015 ◽  
Vol 3 (1) ◽  
pp. 41-45 ◽  
Author(s):  
D. S. Chu ◽  
D. L. Sellers ◽  
M. J. Bocek ◽  
A. E. Fischedick ◽  
P. J. Horner ◽  
...  

Enzymatically-responsive bivalirudin polymers loaded in thermoresponsive hydrogels mediate localized therapeutic peptide delivery in spinal cord injuries. These materials respond to upregulated remodelling enzymes to release therapeutic peptide into injured tissue.


2009 ◽  
Vol 134 (1) ◽  
pp. 11-17 ◽  
Author(s):  
A.M.M. Sadeghi ◽  
M.R. Avadi ◽  
Sh. Ejtemaimehr ◽  
Sh. Abashzadeh ◽  
A. Partoazar ◽  
...  

2014 ◽  
Vol 17 (1) ◽  
pp. 144-155 ◽  
Author(s):  
Annette Bak ◽  
Dennis Leung ◽  
Stephanie E. Barrett ◽  
Seth Forster ◽  
Ellen C. Minnihan ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 99 ◽  
Author(s):  
David Dahlgren ◽  
Markus Sjöblom ◽  
Mikael Hedeland ◽  
Hans Lennernäs

Permeation enhancers like sodium dodecyl sulfate (SDS) and caprate increase the intestinal permeability of small model peptide compounds, such as enalaprilat (349 Da). However, their effects remain to be investigated for larger low-permeability peptide drugs, such as hexarelin (887 Da). The objective of this single-pass perfusion study in rat was to investigate the effect of SDS at 5 mg/mL and of caprate administered at different luminal concentrations (5, 10, and 20 mg/mL) and pH (6.5 and 7.4). The small intestinal permeability of enalaprilat increased by 8- and 9-fold with SDS at 5 mg/mL and with caprate at 10 and 20 mg/mL but only at pH 7.4, where the free dissolved caprate concentration is higher than at pH 6.5 (5 vs. 2 mg/mL). Neither SDS nor caprate at any of the investigated luminal concentrations enhanced absorption of the larger peptide hexarelin. These results show that caprate requires doses above its saturation concentration (a reservoir suspension) to enhance absorption, most likely because dissolved caprate itself is rapidly absorbed. The absent effect on hexarelin may partly explain why the use of permeation enhancers for enabling oral peptide delivery has largely failed to evolve from in vitro evaluations into approved oral products. It is obvious that more innovative and effective drug delivery strategies are needed for this class of drugs.


2017 ◽  
Vol 46 (21) ◽  
pp. 6553-6569 ◽  
Author(s):  
Handan Acar ◽  
Jeffrey M. Ting ◽  
Samanvaya Srivastava ◽  
James L. LaBelle ◽  
Matthew V. Tirrell

This review discusses self-assembled vehicles as nanoparticles to carry and protect therapeutic peptides through their journeys in the body.


2015 ◽  
Vol 6 (11) ◽  
pp. 1279-1296 ◽  
Author(s):  
Jinjin Zhang ◽  
Swapnil S Desale ◽  
Tatiana K Bronich

1989 ◽  
Vol 256 (1) ◽  
pp. G87-G91 ◽  
Author(s):  
H. H. Lee ◽  
A. S. Prasad ◽  
G. J. Brewer ◽  
C. Owyang

We determined the intestinal site of zinc absorption in humans and investigated the interaction between intestinal absorption of zinc and other solutes using the triple-lumen steady-state perfusion technique. Twenty-one healthy subjects participated in the study. During intestinal perfusion of a balanced electrolyte solution containing 0.1 mM zinc acetate, zinc absorption occurred throughout the entire small intestine. However, the jejunum had the highest rate of absorption (357 +/- 14 nM.min-1.40 cm-1) compared with the duodenum (230 +/- 33 nM.min-1.40 cm-1) and ileum (84 +/- 10 nM.min-1.40 cm-1). Over a range of zinc concentrations infused into the jejunum (0.1, 0.9, and 1.8 mM) there were linear increases in the rate of zinc absorption (P less than 0.05). Intestinal absorption of zinc was significantly stimulated by the addition of glucose (20 mM). Zinc absorption increased from 459 +/- 39 to 582 +/- 45 nM.min-1.40 cm-1 (P less than 0.05). Conversely, zinc (0.9 mM) also enhanced the absorption of glucose, which was increased from 293 +/- 43 to 447 +/- 27 microM.min-1.40 cm-1 (P less than 0.05). The enhanced absorption of zinc or glucose was not accompanied by any increase in absorption of water and sodium. In contrast, increasing the concentration of zinc in the perfusate resulted in decreased absorption of sodium and water in a dose-related manner. In conclusion, our study demonstrated that zinc absorption is concentration dependent and occurs throughout the small intestine. The jejunum has the highest rate of absorption of zinc. The interactions between absorption of zinc and other solutes suggest that the transport process of zinc is carrier mediated.


2019 ◽  
Vol 25 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Saeideh Allahyari ◽  
Yousef Javadzadeh

Protein and peptide delivery systems attract great attention nowadays. They play crucial role in several diseases, but their way of administration has some disadvantages that makes patients dissatisfied. In this study, we choose insulin as a peptide that is used for type I and type II diabetic patients, but injection way of its usage is not suitable in diabetes as a chronic remedy. Although oral way is a needle-free one, but its bioavailability through that would be decreased because of degradation in gastro-intestine and consequently, further dosage should be used to get the desired hypoglycemic effect. Administration of insulin through non-parenteral and less enzymatic pathways, such as intranasal, pulmonary, transdermal, colon and vaginal routes, is new that attracts researchers’ attention considerably. Although the bioavailability of insulin may be lower than the current injection way, but it may be improved by some strategies like the use of permeation enhancers. There are also some limitations in each way, but propagation of them would result in improvement of patients’ quality of life and may cause some economic profits. The objective of this review was to introduce the convenient ways for long term insulin administration with few enzymatic barriers.


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