Synthesis Of N-mPEG-O-quaternized Chitosan Microsphere And Its Controlled Drug Release

Chitosan and poly(ethylene glycol) which both have good biodegradability,biocompatibility and low toxicity are well-used in biomedical field. On the basis ofthe chitosan’s inherent nature, O-quaternized chitosan has permanent positive charge,good solubility and different pH responsibility from chitosan because of theintrodution of the quaternary ammonium group. As a synthetic polymer, PEG hashighly hydrophilic and compliant chain. The polymer modified by PEG haveadvantages of stable surface, extended the circulation time, solubilization and so on.Combining of the advantages of three, N-mPEG-O-quaternized chitosan microsphereshave potential applications in controlled drug release.In this paper, N-mPEG-O-quaternized chitosan was modified by grafting mPEG-CHO onto O-quaternized chitosan on the Schiff base reaction used sodiumborohydride as reducing agent. DVS cross-linked N-mPEG-O-quaternized chitosanmicrospheres were prepared by inverse suspension. The experimential results ofsynthesis indicated the reaction can be taken place under mild conditions. Accordingto EA, we could find that the content of PEG and quarternary ammonium group couldbe controlled.Using ketoprofen and5-fluorouracil as model drugs, the drug-loading capacityand release behavior of microsphere has been studied. Compared with CSmicrosphere and O-quaternized chitosan microsphere, the N-mPEG-O-quaternizedchitosan microsphere had best drug-loading capablity, The maximum drug loadingamount of ketoprofen and5-fluorouracil are4.31mg/mg and799.84mg/g. The releasebehavior of two model drugs are similar, N-mPEG-O-quaternized chitosanmicrosphere had brust release in simulated gastric solution and sustained-release inmimic intestinal solution. It seemed quarternary ammonium group and drug itself haddifferent forms in acidic and alkaline conditions. Together with quarternaryammonium group, the H-bond of PEG and drug made the sustained-release. The pHresponsibility of the drug-loaded QACS-mPEG microsphere has value practicalapplication.