title: Ionotropically cross-linked pH-sensitive IPN hydrogel matrices as potential carriers for intestine-specific oral delivery of protein drugs.
abstract: BACKGROUND
  The oral delivery of proteins and peptide drugs is considered a major challenge. These types of therapeutics are readily degraded, if taken orally, due to the harsh high acidity of stomach and enzymatic attack in the upper small intestinal tract.
  
  
  METHODS
  Water-soluble copolymers of sodium acrylate (AAs) grafted onto carboxymethyl cellulose (CMC) were prepared and characterized using Fourier transform spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained graft copolymers were then used in a combination with sodium alginate to develop a new series of pH-sensitive interpenetrating polymeric network (IPN) hydrogels through ionotropic gelation with divalent ions (Ca(2+)). Morphology of the developed hydrogels was investigated using SEM. Swelling characteristics, at distinct compositions, were also studied at 37°C in two consecutive buffer solutions of pH 2.1 and 7.4 (similar to that of gastric and intestinal fluids, respectively). The release profiles of bovine serum albumin, as a model protein, from test IPN hydrogel films were studied in simulated gastric and intestinal fluids. In addition, the drug release process was confirmed by means of SEM.
  
  
  RESULTS
  Swelling studies of the developed IPN hydrogels at different pH values confirmed their pH-sensitive nature. The equilibrium swelling extents of the hydrogels were found to be dependent on the grafting yield of CMC/AAs graft copolymer. The IPN hydrogels attained equilibrium swelling percentages in the range 445-740%. In addition, the amount of bovine serum albumin released within 2 hours in pH 2.1 was relatively low (less than 18.1%). This amount increased up to 68% after 8 hours in pH 7.4.
  
  
  CONCLUSIONS
  From the obtained preliminary data, it seems that the IPN hydrogels developed in this contribution can be tailored to act as good potential carriers for oral delivery of protein drugs. These hydrogels showed a promising protection of protein drugs from the harsh acidity of stomach and, at the same time, they conferred sustained drug release in the intestinal fluid.
authors.affiliation: Chemistry Department, Faculty of Science, Polymer Laboratory, Mansoura University, Mansoura, Egypt. sherbiny@mail.utexas.edu
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Sherbiny
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salama
authors.forename: Ali A
authors.initials: AA
authors.lastname: Sarhan
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000284:Administration, Oral; D002118:Calcium / Q000737:chemistry; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005750:Gastric Juice / Q000378:metabolism; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D000179:Acrylates; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D012710:Serum Albumin, Bovine; C036658:acrylic acid; D002266:Carboxymethylcellulose Sodium; D002118:Calcium