Study On A Novel PH-sensitive Hydrogel For Oral Delivery Of Protein Drugs

N,O-carboxymethyl chitosan (NOCC) which is more soluble in the neutral media was synthesized by carboxymethylizing chitosan by using the monochloroacetic acid. N-m-Polyethylene-glycol-ether-aldehyde (mPEG-CHO) grafted NOCC was synthe- sized by two steps: The mPEG-CHO and NOCC reacted together to form the Schiff's base which was deoxidized sequently. The structures of the products were characte- rized by FTIR and 1H-NMR and the synthesis process was optimized. The degree of NOCC substitution (DS) was calculated by potentiometric titration. The solubility of NOCC was investigated to be better than that of chitosan when DS was increased.Chitosan derivation and Alginate were chosen as the candidates to construct the matrix of the semi-interpenetrating polymeric network (semi-IPN) due to their exce- llent properties such as biocompatibility, pH-sensitivity. PEG was added in the hydrogel systems in two manners (by mixing the PEG to the hydrogel or grafting the m-PEG-CHO to NOCC). Bovine serum albumin (BSA) as a model of protein drugs was encapsulated in the hydrogel network by in situ-fabrication. The diameter of the prepared drug-loaded beads was 2.0 mm to 3.0 mm. The drug was proved to be successfully encapsulated and uniformly distributed in the crosslinked networks by employing fluorescence-microscope and differential scanning calorimetery (DSC). The drug association efficiency (90.07%) and the drug loading capacity (14.72%) can be largely increased by varying the composition of the hydrogels. The cumulative drug release was also investigated. The amount of BSA released at pH1.2 was relatively low (20%), while that released at pH7.4 increased significantly (80%). These results suggest that the novel pH-sensitive hydrogel could be a suitable polymeric carrier for site-specific protein drug delivery in the intestine.