ABSTRACT
OBJECTIVE: To develop a kind of multifunctional targeting epirubicin liposomes for the treatment of brain tumor, to characterize their physicochemical properties, and to observe their targeting effects on the brain microvascular endothelial cells (BM-VECs) and on the brain glioma cells. METHODS: The 2-amino-2-deoxy-β-Z)-glucopyranose(NH2-Glu) was used as a targeting molecule and conjugated with a cholesterol-polyethylene glycol derivative (Chol-PEG2000-NHS) for obtaining the targeting functional material aimed at targeting to glucose transporter-1 (Glut-1) on the BMVECs of blood-brain barrier and further targeting to the glioma cells. To prepare the multifunctional targeting epirubicin liposomes, the targeting functional material was modified onto the surface of liposomes, and epirubicin was loaded into the core of liposomes as the anticancer drug. The encapsulation efficiency, particle size, polydispersity indexes and Zeta potential of the liposomes were measured, their cellular uptakes were performed on the BMVECs and the glioma cells. The inhibitory effect was performed on the glioma cells. RESULTS: The analysis by MALDI-TOF-MS demonstrated that the targeting functional material, Chol-PEG2000-Glu, was successfully synthesized. The multifunctional targeting epirubicin liposomes were prepared, and had an average particle size of approximately 125 nm, and were negatively charged. The encapsulation efficiency of epirubicin in the liposomes was about 93%. Results from flow cytometry indicated that the multifunctional targeting epirubicin liposomes had the highest cellular uptakes by BMVECs and by two kinds of brain glioma cells as compared with no-targeting epirubicin liposomes. The cytotoxic study showed that the multifunctional targeting epirubicin liposomes had the strongest inhibitory effect to brain glioma cells as compared with free epirubicin or no-targeting epirubicin liposomes. CONCLUSION: A new targeting material (Chol-PEG2000-Glu) and the multifunctional targeting epirubicin liposomes are developed, and the multifunctional targeting epirubicin liposomes exhibit the potential lortransporting across the blood-brain barrier (BBB), and selectively inhibiting the brain glioma cells.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of di-butyl phthalate (DBP) on the reproductive system of adolescent male rats.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats aged 5 weeks were assigned to receive corn oil (vehicle control) or DBP orally at 10, 100 and 500 mg/(kg x d) for 30 days. After the exposure, the testis, epididymis, liver and pituitary of the rats were weighted and their ratios to the body weight obtained. Histopathological changes of the testis and epididymis were examined by Hematoxylin-eosin staining, the levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum were measured by radioimmunoassay, and the relative mRNA expressions of the steroidogenesis acute regulatory protein (StAR), proliferating cell nuclear antigen (PCNA), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and scavenger receptor (SR) were detected by real-time quantitative RT-PCR.</p><p><b>RESULTS</b>DBP induced significant histopathological changes in the testicular tissue at 100 and 500 mg/(kg x d), and decreased the testicular and epididymal weights, inhibited the mRNA expressions of StAR and PCNA, reduced the levels of T and LH, and elevated the level of FSH at 500 mg/(kg x d). At the dose of 10 mg/(kg x d), DBP increased serum LH and FSH and the mRNA expression of P450scc. While the SR mRNA expression showed no significant changes in all the groups.</p><p><b>CONCLUSION</b>High level of DBP has apparent toxic effect on reproductive system of male rats. Low - dose DBP can increase the level of serum gonadotropin LH and affect the mRNA expression of P450scc in the testis.</p>