Studies On Folate Receptor Targeted PH Sensitive Antitumor Drug Delivery System

Targeted drug delivery system (TDDS) is a novel commendable type of pharmacology preparation which can concentrate the drug in diseased organs, tissues, cells or intracellular organelle. Targeted therapy can significantly increase the drug concentration in treatment site, reduce the dosage and lower side effects. Folate targeted drug delivery system has a good tumor targeting effect and it is one of the ideal drug delivery methods for anticarcinogen. This drug delivery system conjugated with some functional hydrophilic polymer block possess many advantages, such as high efficiency, low toxicity, high specificity and long circulation, thus has attracted extensive attention recently.Object:A novel drug carrier based on folate conjugated pH sensitive polymer (F-PEOz-DSPE) was synthesized and used as liposomes carrier materials. The property of liposome was studied employing doxorubicin as model drug. Result showed the drug delivery system was high efficient and low toxic. The in vitro target-specificity and pH sensitivety of liposome were also evaluated.Method:A novel folic acid conjugated pH sensitive polymer (F-PEOz-DSPE) was synthesized. Doxorubicin loaded liposome was prepared by means of ammonium sulfate gradients method;the particle size and encapsulation efficiency was determined. A RP-HPLC method was established to determine the drug content in doxorubicin hydrochloride liposomes. The physiochemical and release property was also characterized. The preliminary pharmacodynamics property was tested by in vitro assay.Result:â‘ PEOz-DSPE and F-PEOz-DSPE with different molecular weight was synthesized. The structure and molecular weight was confirmed by 1H NMR, FT-IR, GPC, UV, and ESI-MS assay.â‘¡The doxorubicin loaded liposome had particle size of ca. 100 nm with narrow size distribution and the encapsulation efficiency was higher than 90%. The release profile of doxorubicin lispome was faster under pH 5.0 than that in neutral medium, implying the PEOz segment could provide pH sensitivity to the liposome.â‘¢The content of doxorubicin in liposome could be determined precisely and conveniently by the built RP-HPLC method.â‘£In vitro cell test showed that this novel drug delivery system possessed tumor targeting specificity and pH sensitivety, which could facilitate the antitumor effect of the anticarcinogen.Conclusion:The synthesized F-PEOz-DSPE is consistent with the designed structure. Doxorubicin loaded liposome prepared by F-PEOz-DSPE has ideal particle size, size distribution and encapsulation efficiency. The liposome, possessing tumor targeting specificity and pH sensitivity, is a promising candidate for novel antitumor drug delivery system.