Polyanion / Gender Chitosan Complex For Protein Drug Ph-responsive Release

Drug controlled release is one of the most important task in pharmaceutics. A great progress in this field had been made since 1960', and kinds of materials and systems have been shown to satisfy the variant requirements of different types of drug, wide range of drug delivery environment. In these systems, the biodegradable polymeric particle is one of the most important systems.Our project here is to design and synthesize a novel class of biodegradable natural polymeric complex system for pH-sensitive release of protein drugs. The major work focused on the design of polymeric materials, characterization, protein entrapment and drug release assessment in vitro.In this paper, the ampholytic chitosan, N-carboxyethyl chitosan (CEC), with various isoelectric points was synthesized by Michael reaction of acrylic acid with chitosan. In comparison with the unmodified chitosan, CEC displayed enhanced water-solubility and dramatically accelerated enzymatic degradation. High degree of substitution (DS) of acrylic acid favored rapid degradation rate. By turbidimetric titration and fluorescence study, it was revealed that CEC formed complexes with either polyanions or Bovine serum albumin (BSA) within a certain pH range, polyanions include herapin (HP) and hyaluronon (HA). The HP/CEC/BSA and HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment.It was found that, on the one hand, polyanions, CEC and BSA can form complexes within a certain pH range and the critical pH value for complexation (pHφ) is related to the DS of acrylic acid. The larger the DS, the higher pHφ value. On the other hand, the entrapment efficiency of BSA is very high, approaching 100%, and BSA release is extremely pH-dependent. The transition of BSA release can occur within rather narrow pH range (<0.4 pH unit). The critical pH value for the transition (pHφ) can also be modulated byDS. It seems that BSA release transition is correlated with polyanions/CEC/BSA complexation. Meanwhile, BSA release from the complexes is affected by pH, ionic strength, DS of CEC and molecular weight (MW) of HA. In addition, HA/CEC/BSA can retain BSA in complexes and extend release time better than HP/CEC/BSA. By selecting high MW HA and CEC with low DS, BSA could be released from the complexes at a pseudo zero order for up to 30 days.