Rectal Delivery of Insulin Using a Bioadhesive Hydrogel Preparation Containing Lauric Acid as an Enhancer in Rats

Uchida, Takahiro; Sakakibara, Sadako; Toida, Yuka; Nagareya, Noriko; Yasuda, Noriko; Matsuyama, Kenji

doi:10.1211/146080899128735289

Cited by 6 publications

(2 citation statements)

References 6 publications

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“…Additional delivery sites that have been explored for their accessibility include the rectal, vaginal and ocular mucosas. Protein delivery via the rectal mucosa has been investigated by Uchida et al (1999). An advantage of rectal delivery is the avoidance of enzymatic degradation since there can be direct protein absorption by the lymphatic system (Owens et al, 2003).…”

Section: Drug Delivery Routesmentioning

confidence: 99%

Impact of absorption and transport on intelligent therapeutics and nanoscale delivery of protein therapeutic agents

Peppas

Carr

2009

Chemical Engineering Science

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The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist.Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists.

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Section: Drug Delivery Routesmentioning

confidence: 99%

Impact of absorption and transport on intelligent therapeutics and nanoscale delivery of protein therapeutic agents

Peppas

Carr

2009

Chemical Engineering Science

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“…In particular the oral route, which is the most convenient and easy medication, is the less suitable for protein molecules. Most peptide drugs show very low oral activity as a consequence of the degradation by gastrointestinal tract enzymes and the poor permeability of the intestinal mucosa. , Alternative medications, such as nasal, pulmonary, , rectal, buccal, vaginal, and transdermal, have been investigated. But it has been shown that protease activities in the homogenates of the nasal, buccal, rectal, and vaginal mucosa of rabbits are substantial and quite comparable to those found in the intestinal mucosa …”

Section: Introductionmentioning

confidence: 99%

Nanoaggregates Based on New Poly-Hydroxyethyl-Aspartamide Copolymers for Oral Insulin Absorption

et al. 2013

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The aim of this work was to produce copolymers with an appropriate hydrophilic/hydrophobic balance able to form nanoaggregates with protein molecules and to be used as ideal materials in the field of oral peptide/protein delivery. New anionic polymers obtained by the conjugation of carboxy-bearing ligands, like succinic anhydride and/or cysteine, to hydrophobized α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) copolymers have been synthesized and characterized. Starting copolymer was synthesized by the partial derivatization of hydroxyl groups on the PHEA backbone with butylamine (C4) (obtaining the PHEA-C4 copolymer, bearing a butyl moiety). The consecutive reaction of PHEA-C4 with succinic anhydride permitted the PHEA-C4-S copolymer to be obtained, bearing pendant carboxylic groups as well. Finally, part of the pendant carboxylic groups were conjugated to cysteine via an amidic bond, obtaining PHEA-C4-S-Cyst. All synthesized copolymers, PHEA-C4, PHEA-C4-S, and PHEA-C4-S-Cyst, exhibit the ability to interact with insulin in aqueous medium forming nanoaggregates. Physical characterization of prepared insulin/copolymer nanoaggregates was carried out by means of turbidimetric measurements and DLS analysis. These studies demonstrated that synthesized copolymers form colloidal aggregates in the presence of insulin, with size ranging between 62 and 216 nm. Stability studies in the presence of the peptidase α-chymotrypsin showed also the ability of synthesized copolymers to increase insulin stability against enzymatic degradation in the order PHEA-C4-S-Cyst > PHEA-C4-S > PHEA-C4. Moreover, in dosage form such as tablets, the synthesized copolymers displayed the properties to prolong disintegration time and control release of the embedded peptide drug into media mimicking intestinal fluids. The administration of insulin in the presence of PHEA-C4-S-Cyst and PHEA-C4-S copolymers resulted in the ability to provoke a certain absorption of insulin and consequently to induce in vivo hypoglycemic effects on rats after oral administration with respect to free insulin. In particular, the hypoglycemic effect shown by PHEA-C4-S/insulin nanoaggregates was equal to almost 30% of the effect observed after the administration of insulin by conventional subcutaneous administration and about 20% in the case of PHEA-C4-S-Cyst/insulin nanoaggregates. These copolymers are good starting materials for the preparation of an oral dosage form of proteins.

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Alternative Routes of Insulin Delivery

Owens

Bolli

Zinman

2003

International Textbook of Diabetes Mellitus

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Identification of the pancreas as the site of the defect in diabetes mellitus by von Mehring and Minkowski in 1889 led eventually to the identification and successful extraction of insulin in 1921 by Banting and Best. The availability of insulin for therapy shortly afterwards dramatically changed the lives of patients with diabetes who previously had a life expectancy of less than 2 years. In the 80 years since, major benefits have accrued. In the year 2000 alone, it is estimated that about 4.8 million years of life were gained for patients with type 1 diabetes as a result of insulin treatment, assuming a life expectancy of 1.5 years in its absence and a global prevalence of 5.1 million. Since insulin was first introduced into clinical practice there have been major developments in its production, purification, pharmaceutical formulation, and methods of delivery. However, despite these advances, microvascular and premature macrovascular complications persist as the main cause of morbidity and mortality in both type 1 and type 2 diabetes and represent a constant reminder that current therapeutic and management strategies, for the vast majority of our patients, remain woefully inadequate. In this chapter, we describe the many attempts made to develop alternative, less invasive routes for the delivery of insulin while focusing on recent progress achieved with inhaled insulins, which may provide the first opportunity for at least partial independence from subcutaneous injections.

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Rectal Delivery of Insulin Using a Bioadhesive Hydrogel Preparation Containing Lauric Acid as an Enhancer in Rats

Cited by 6 publications

References 6 publications

Impact of absorption and transport on intelligent therapeutics and nanoscale delivery of protein therapeutic agents

Impact of absorption and transport on intelligent therapeutics and nanoscale delivery of protein therapeutic agents

Nanoaggregates Based on New Poly-Hydroxyethyl-Aspartamide Copolymers for Oral Insulin Absorption

Alternative Routes of Insulin Delivery

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