Study Of Poly(lactic-co-glycolic Acid) Microspheres Containing ADM For Injection

Adriamycin (ADM, Doxorubicin, DOX), one of the anthracycline ring antibiotics with great anti-tumor activity against a variety of tumors, has the ability to interact with DNA and consequently inhibit important cellular functions. But its therapeutic potential has been restricted by its dose-limited cardio-toxicity and by the resistance developed by the tumor cells to this molecular after some time of treatment. In order to eliminate the limitations in clinical applications, some new drug delivery systems have to be found. Of this form, more and more researchers pay attention to the microspheres formed with biodegradable materials, such as poly(lactic-co-glycolic acid)(PLGA).Adriamycin PLGA microspheres were prepared by double emulsion method. The optimum preparation conditions were selected with orthogonal design combined with multi-index test. Three independent variables include the concentration of PLGA, the ratio of inner water phase and oil phase, the concentration of PVA. We investigated the mean diameter, span of dispersity, encapsulation efficiency, drug loading, initial burst of the microspheres. The repeated tests of the optimized formulation proved that the technology and formulation are stable and repeatable. The release kinetics of microspheres in vitro could be characterized by Higuchi equation. We studied the correlation of short-term accelerated release(50℃) with long-term conventional release(37℃)in vitro. The experiments indicated that accelerated release correlates with conventional release. We used γ-ray radiation as sterilization method, and this method was effective and feasible.Then their release behavior in vivo was investigated by measuring residual dosage after subcutaneous injection in rats. Further we established an HPLC method...