Chemical Modification of Alginate for Controlled Oral Drug Delivery.

Here, we report two methods that chemically modify alginate to achieve neutral-basic pH sensitivity of the resultant hydrogel. The first method involves direct amide bond formation between alginate and 4-(2-aminoethyl)benzoic acid. The second method that arose out of the desire to achieve better control of the degradation rate of the alginate hydrogel involves reductive amination of oxidized alginate. The products of both methods result in a hydrogel vehicle for targeted delivery of encapsulated payload under physiological conditions in the gastrointestinal tract. Two-dimensional diffusion-ordered spectroscopy and internal and coaxial external nuclear magnetic resonance standards were used to establish chemical bonding and percent incorporation of the modifying groups into the alginate polymer. The hydrogel made with alginate modified by each method was found to be completely stable under acidic pH conditions while disintegrating within minutes to hours in neutral-basic pH conditions. We found that, while alginate oxidation did not affect the β-d-mannuronate/α-l-guluronate ratio of alginate, the rate of disintegration of the hydrogel made with oxidized alginate was dependent upon the degree of oxidation.