Wheat Germ Agglutinin Functionalized Complexation Hydrogels for Oral Insulin Delivery

Abstract

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.

Calcium alginate nanocarriers as possible vehicles for oral delivery of insulin

“…In this way, these two unfavourable consequences lead to poor therapeutic efficiency and need further efforts. In order to resolve these complexities some strategies have been suggested like use of pH change between the stomach and the small intestine within the GI tract [29] and exploitation of the bacterial enzymes localised within the colon [30]. The influence of pH on the water sorption capacity of the alginate nanoparticles and quantity of the released insulin has been examined by conducting swelling and release experiments at pH 1.2 and 7.4 which, respectively, represent the acidic and alkaline environments of stomach and blood.…”

Nanodiamond–insulin complexes as pH-dependent protein delivery vehicles

“…The oral delivery of dextran sulfate/chitosan-based nanoparticles has also been explored in diabetic rats to increase pharmacological availability [31]. Furthermore, hydrogels based on poly(methacrylic acid-grafted-ethylene glycol) and wheat germ agglutinin functionalized poly(methacrylic acid-grafted-ethylene glycol) have also been explored for the oral delivery of insulin with pH-dependent release characteristics [32].…”

pH‐Responsive Poly(methacrylic acid)‐Grafted Hollow Silica Vesicles

“…[7][8][9] For example, in humans the pH changes from below 3 in the stomach to 7 in the intestine, so pH-responsive vesicles with good integrity at pH < 3, but release channels at pH > 7 are promising for the oral delivery of some drugs, such as insulin. [10] One versatile approach to pH-responsive vesicles is to integrate polyelectrolytes into the vesicle membranes, and poly-(acrylic acid) is one type of polyelectrolytes that has pH-responsive properties resulting from pH-induced ionisation and deionisation. [7][8][9][11][12][13] Polymer vesicles containing poly-(acrylic acid) in the membranes showed pH-dependent permeability caused by changes in the solubility of poly(acrylic acid) in aqueous solution; the channels in the vesicles membranes were sealed at pH < 4.0, but were open at pH > 8.0.…”