Oral delivery of insulin using pH‐responsive complexation gels

Lowman, Anthony M.; Morishita, Mariko; Kajita, Masako; Nagai, Tsuneji; Peppas, Nicholas A.

doi:10.1021/js980337n

Cited by 370 publications

(236 citation statements)

References 17 publications

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“…In some of the experiments, a small increase in BGL above the baseline is observed. This increase may be attributed to metabolic changes and endogenous secretion of glucagon in the diabetic rats due to stress in the animals during blood sampling (38,39). In both the p.o.…”

Section: Resultsmentioning

confidence: 99%

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

et al. 2007

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Purpose. Colloidal metallic systems have been recently investigated in the area of nanomedicine. Gold nanoparticles have found themselves useful for diagnostic and drug delivery applications. Herein we have reported a novel method for synthesis of gold nanoparticles using a natural, biocompatible and biodegradable polymer; chitosan. Use of chitosan serves dual purpose by acting as a reducing agent in the synthesis of gold nanoparticles and also promotes the penetration and uptake of peptide hormone insulin across the mucosa. To demonstrate the use of chitosan reduced gold nanoparticles as carriers for drug delivery, we report herein the transmucosal delivery of insulin loaded gold nanoparticles. Materials and Methods. Gold nanoparticles were prepared using different concentrations of chitosan (from 0.01% w/v up to 1% w/v). The gold nanoparticles were characterized for surface plasmon band, zeta potential, surface morphology, in vitro diffusion studies and fluorescence spectroscopy. The in vivo studies in diabetic male Wistar rats were carried out using insulin loaded chitosan reduced gold nanoparticles.Results. Varying concentrations of chitosan used for the synthesis of gold nanoparticles demonstrated that the nanoparticles obtained at higher chitosan concentrations (>0.1% w/v) were stable showing no signs of aggregation. The nanoparticles also showed long term stability in terms of aggregation for about 6 months. Insulin loading of 53% was obtained and found to be stable after loading. Blood glucose lowering at the end of 2 h following administration of insulin loaded gold nanoparticles to diabetic rats was found to be 30.41 and 20.27% for oral (50 IU/kg) and nasal (10 IU/kg), respectively. Serum gold level studies have demonstrated significant improvement in the uptake of chitosan reduced gold nanoparticles. Conclusions. The synthesis of gold nanoparticles using a biocompatible polymer, chitosan would improve its surface properties for binding of biomolecules. Our studies indicate that oral and nasal administration of insulin loaded chitosan reduced gold nanoparticles has led to improved pharmacodynamic activity. Thus, chitosan reduced gold nanoparticles loaded with insulin prove to be promising in controlling the postprandial hyperglycemia.

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Section: Resultsmentioning

confidence: 99%

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

et al. 2007

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“…It has been stated earlier that the enteric polymers are generally used either to protect the acid-labile drugs (e.g., peptides and penicillin-G) from the harsh environment of the stomach or to avoid the contact of the gastric mucosa with the gastric-irritant drugs (e.g., ibuprofen, indomethacin), which might lead to gastric mucosa perforations. Akiyama and co-workers developed such an enteric system using poly(acrylic acid) product, which inhibited the hydrolytic activity of trypsin [53]. The oral delivery of insulin employing the use of enteric polymers is gaining importance [54].…”

Section: Matrix Systemmentioning

confidence: 99%

Polymeric Hydrogels: Characterization and Biomedical Applications

Pal

Banthia

Majumdar

2009

Designed Monomers and Polymers

300

182

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Hydrogels are cross-linked polymeric networks, which have the ability to hold water within the spaces available among the polymeric chains. The hydrogels have been used extensively in various biomedical applications, e.g., drug delivery, cell carriers and/or entrapment, wound management and tissue engineering. Though far from extensive, this article has been devoted to study the common methods used for the characterization of the hydrogels and to review the range of applications of the same in health care.

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“…Lowman et al 5 demonstrated the potential of these environmentally sensitive complexation hydrogels to be used as a carrier for oral protein delivery, by delivering insulin to diabetic rats and lowering blood glucose levels. In addition, Madsen and Peppas 6 determined that the calcium binding properties of ionized MAA inhibit some proteolytic degradation of the released protein, therefore increasing the amount of bioactive protein transported across the epithelial layer.…”

Section: Introductionmentioning

confidence: 99%

Wheat Germ Agglutinin Functionalized Complexation Hydrogels for Oral Insulin Delivery

2008

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Insulin was loaded into hydrogel microparticles after two hours with loading efficiencies greater than 70% for both poly(methacrylic acid-grafted-ethylene glycol) (P(MAA-g-EG)) and poly(methacrylic acid-grafted-ethylene glycol) functionalized with wheat germ agglutinin (P(MAA-g-EG) WGA). The pH-responsive release results demonstrated that the pH shift from the stomach to the small intestine can be used as a physiologic trigger to release insulin from P(MAA-g-EG) and P(MAA-g-EG) WGA microparticles, thus limiting release of insulin into the acidic environment of the stomach. Microplates were successfully treated with PGM to create a surface that allowed for specific binding between mucins and lectins. The 1% PGM treatment followed by a 2 h BSA blocking step gave the most consistent results when incubated with F-WGA. In addition, the PGM-treated microplates were shown to create specific interactions between F-WGA and the PGM by use of a competitive carbohydrate. The 1% PGM treated microplates were also used to show that adhesion was improved in the P(MAA-g-EG) WGA microparticles over the P(MAA-g-EG) microparticles. The interaction between the PGM-treated microplate and P(MAA-g-EG) WGA was again shown to be specific by adding a competitive carbohydrate, while the interaction between P(MAA-g-EG) and the PGM-treated microplate was nonspecific. Cellular monolayers were used as another method for demonstrating that the functionalized microparticles increase adhesion over the nonfunctionalized microparticles. This work has focused on improving the mucoadhesive nature of P(MAA-g-EG) by functionalizing these hydrogel carriers with wheat germ agglutinin (WGA) to create a specific mucosal interaction and then evaluating the potential of these carriers as oral insulin delivery systems by in vitro methods. From these studies, it is concluded that the addition of the WGA on the microparticles produces a specific adhesion to carbohydrate-containing surfaces and that P(MAA-g-EG) WGA shows great promise as an oral insulin delivery system.

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Oral delivery of insulin using pH‐responsive complexation gels

Cited by 370 publications

References 17 publications

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

Polymeric Hydrogels: Characterization and Biomedical Applications

Wheat Germ Agglutinin Functionalized Complexation Hydrogels for Oral Insulin Delivery

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