ABSTRACT
A novel method using a temperature-sensitive polymer (methylcellulose) to thermally gel aqueous alginate blended with distinct salts (CaCl2, Na2HPO4, or NaCl), as a pH-sensitive hydrogel was developed for protein drug delivery. It was noted that the salts blended in hydrogels may affect the structures of an entangled network of methylcellulose and alginate and have an effect on their swelling characteristics. The methylcellulose/alginate hydrogel blended with 0.7 M NaCl (with a gelation temperature of 32 degrees C) demonstrated excellent pH sensitivity and was selected for the study of release profiles of a model protein drug (bovine serum albumin, BSA). In the preparation of drug-loaded hydrogels, BSA was well-mixed to the dissolved aqueous methylcellulose/alginate blended with salts at 4 degrees C and then gelled by elevating the temperature to 37 degrees C. This drug-loading procedure in aqueous environment at low temperature may minimize degradation of the protein drug while achieving a high loading efficiency (95-98%). The amount of BSA released from test hydrogels was a function of the amount of alginate used in the hydrogels. The amount of BSA released at pH 1.2 from the test hydrogel with 2.5% alginate was relatively low (20%), while that released at pH 7.4 increased significantly (86%). In conclusion, the methylcellulose/alginate hydrogel blended with NaCl could be a suitable carrier for site-specific protein drug delivery in the intestine.
Subject(s)
Alginates/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Hydrogels/chemistry , Methylcellulose/chemistry , Hydrogen-Ion Concentration , TemperatureABSTRACT
The study was undertaken to examine the degree of tissue fixation by reuterin, a natural compound produced by Lactobacillus reuteri, at distinct fixation conditions (pH, temperature, and fixative concentration). Additionally, the rate of tissue fixation by reuterin was investigated using glutaraldehyde as a control. It was found by the Fourier transformed infrared spectroscopy and nuclear magnetic resonance spectroscopy that both mono- and di-aldehyde reuterin oligomers may be present in the acidic and basic aqueous reuterin solutions. Therefore, reuterin may crosslink biological tissues as glutaraldehyde (a di-aldehyde agent). The degree of tissue fixation by reuterin is significantly affected by its fixation conditions. Generally, with increasing the pH, temperature, or fixative concentration, the reduction in free-amino-group content, denaturation temperature, tensile strength, and resistance against enzymatic degradation of the reuterin-fixed tissue increased significantly. Also, the rate of tissue fixation by reuterin is significantly slower than that by glutaraldehyde. However, after fixation, it was noted that the reuterin-fixed tissue has comparable free-amino-group content, denaturation temperature, tensile strength, and resistance against enzymatic degradation as the glutaraldehyde-fixed tissue.
