Insulin and the gastrointestinal tract

Saffran, Murray; Pansky, Ben; Budd, G. C.; Williams, Frederick

doi:10.1016/s0168-3659(96)01578-7

Cited by 67 publications

(31 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transport of nutrients across the cell layer and into the blood stream can occur via four different transport mechanisms from one side of the cellular barrier to the other. 9,11 The first mechanism is transcellular and is primarily used by small molecules. The molecule diffuses from one side of the barrier, through the cell, and to the other side.…”

Section: Discussionmentioning

confidence: 99%

Oral Chemotherapeutic Delivery: Design and Cellular Response

Blanchette

Peppas

2005

Ann Biomed Eng

View full text Add to dashboard Cite

The development of carriers to deliver a variety of cancer therapeutics orally would represent a significant advance in the treatment of this disease. This system is based on hydrophilic polymer carriers to deliver therapeutic agents to the upper region of the small intestine in response to the pH increase when passing from the stomach. Methacrylic acid (MAA) and ethylene glycol (EG) combined in a 1:1 molar ratio were reacted to form P(MAA-g-EG) nanospheres by UV-initiated free radical polymerization. Bleomycin was added prior to polymerization to allow in situ polymerization loading. Release studies were carried out in conditions to model the environment of the stomach and small intestine. Results showed that bleomycin is preferentially released at a higher pH due to the increased mesh size of the swollen hydrogel carrier. The potential cytotoxicity of bleomycin on the small intestine was investigated with the use of Caco-2 cells (human colon adenocarcinoma). Cytotoxicity studies showed maintenance of both viability and proliferation. The presence of the nanospheres decreases the transepithelial electrical resistance across Caco-2 cell monolayers. Complexation hydrogels are promising carriers to expand the number of chemotherapeutics capable of being administered orally.

show abstract

Section: Discussionmentioning

confidence: 99%

Oral Chemotherapeutic Delivery: Design and Cellular Response

Blanchette

Peppas

2005

Ann Biomed Eng

View full text Add to dashboard Cite

show abstract

“…For insulin, oral formulations would provide the hormone directly to the liver by the hepatic portal circulation. This will be a major advantage because this pathway mimics the physiological traffic of the hormone when it is secreted by the pancreas of healthy individuals (294). However, mucosal routes are extremely challenging for the administration of peptides and proteins because these generally hydrophilic macromolecules are unable to overcome mucosal barriers by themselves and are degraded before they can reach the blood stream.…”

Section: Application To Metabolic Diseasesmentioning

confidence: 99%

Nanotechnology: Intelligent Design to Treat Complex Disease

2006

View full text Add to dashboard Cite

The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

show abstract

“…The major problem is the inactivation of insulin by digestive enzymes in the gastrointestinal (GI) system, mainly in the stomach and the proximal regions of the small intestine. [3][4][5][6][7][8][9][10] This can be overcome by designing carriers which can protect the insulin from the harsh environments of the stomach before releasing the drug into more favorable regions of the GI tract, specifically the colon. [4][5][6][7][8][9][10][11][12][13] Additionally, researchers have attempted to incorporate protease inhibitors into oral insulin formulations which serve to prevent insulin degradation by the proteolytic enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10] This can be overcome by designing carriers which can protect the insulin from the harsh environments of the stomach before releasing the drug into more favorable regions of the GI tract, specifically the colon. [4][5][6][7][8][9][10][11][12][13] Additionally, researchers have attempted to incorporate protease inhibitors into oral insulin formulations which serve to prevent insulin degradation by the proteolytic enzymes. 4,[7][8][9][10]12,14 The other major barrier is the slow transport of insulin across the lining of the colon into the blood stream.…”

Section: Introductionmentioning

confidence: 99%

Oral delivery of insulin using pH‐responsive complexation gels

Lowman

Morishita

Kajita

et al. 1999

Journal of Pharmaceutical Sciences

370

222

View full text Add to dashboard Cite

The goal of oral insulin delivery devices is to protect the sensitive drug from proteolytic degradation in the stomach and upper portion of the small intestine. In this work, we investigate the use of pH-responsive, poly(methacrylic-g-ethylene glycol) hydrogels as oral delivery vehicles for insulin. Insulin was loaded into polymeric microspheres and administered orally to healthy and diabetic Wistar rats. In the acidic environment of the stomach, the gels were unswollen due to the formation of intermolecular polymer complexes. The insulin remained in the gel and was protected from proteolytic degradation. In the basic and neutral environments of the intestine, the complexes dissociated which resulted in rapid gel swelling and insulin release. Within 2 h of administration of the insulin-containing polymers, strong dose-dependent hypoglycemic effects were observed in both healthy and diabetic rats. These effects lasted for up to 8 h following administration.

show abstract

Insulin and the gastrointestinal tract

Cited by 67 publications

References 16 publications

Oral Chemotherapeutic Delivery: Design and Cellular Response

Oral Chemotherapeutic Delivery: Design and Cellular Response

Nanotechnology: Intelligent Design to Treat Complex Disease

Oral delivery of insulin using pH‐responsive complexation gels

Contact Info

Product

Resources

About