Preparation of dextran nanogel conjugates of HCPT with acid-sensitive spacer and its properties / 中国药学杂志

ABSTRACT

OBJECTIVE: To synthesize a new drug delivery system of polyaldehyde Dex coupled with SA-10-HCPT and to study the HCPT release in vitro and the anti-tumor activity in vivo. METHODS: The new drug delivery system was prepared by polyaldehyde Dex coupled with SA-HCPT, grafted with mPEG-adipic dihydrazide monohydrazone and cross-linked with adipic dihydrazide. RESULTS: The conjugate formed micelle with a diameter of 100 nm in water,which could achieve passive targeting of tumor tissue concentration. The drug loading efficiency achieved 5.63%. The drug release processes accorded with kinetic equation Rc=Atn1/(B+Ctn2) in the buffer solution. The release rate of HCPT from this conjugate in pH 5.4 buffer was much higher than that in the environment of pH 7.4 and pH 4.5. The tumor inhibition of the conjugate was similar to that of HCPT while the toxicity in vivo was significantly reduced. CONCLUSION: The structure of the conjugate is unstable in acidic environment, and the drug is released pH-sensitively. The mice survival rate is significantly improved because of the significant slow-release property. Therefore, the conjugate can be developed as a novel prodrug.