ABSTRACT
This study was conducted to produce pectin-doxorubicin conjugate (PDC) nanosuspensions by high-pressure homogenization, and investigating the physico-chemical properties, the cumulative release rate in vitro and in vivo, and the anti-tumor activity. The major production parameters such as pressure, cycle numbers and types of stabilizers on the mean particle size and polydispersity index (PI) of PDC nanosuspensions were investigated. The cumulative release rate in phosphate buffer saline (PBS) at pH 5.1 or 7.0 were studied. The concentration of doxorubicin (DOX) in plasma of rabbit were recorded after intraperitoneal injection of PDC nanosuspensions (DOX was equivalent to 10mg·kg-1) or DOX (10mg·kg-1). We established an animal model of the nude mice with SKOV3 cell, and injected the PDC nanosuspensions (DOX was equivalent to 10, 5, 2.5 mg·kg-1) in the first day, and observed the growth state of nude mice. The particle size of PDC nanosuspensions was 118.8±6.93 nm, PI was 0.14±0.03, as well as the zeta potential was -27.2±0.36mV. It shows that no drug release was found in PBS at pH 7.4. About 40% cumulative release was determined in PBS at 5.1 after 30 h. The concentration of DOX in plasma of PDC group was 60 ng·mL-1, and was lower than that of DOX group. Compared with control group, high-dose-group decreased the weight of nude mice's ascites tumor and burrknot. PDC nanosuspensions can inhibit the growth of SKOV3 cell line in nude mice. In summary, PDC nanosuspensions are target-specific drugs with high efficiency and low toxicity in the ascites cancer model.