Co-delivery of paclitaxel and doxorubicin using polypeptide-engineered nanogels for combination therapy of tumor.

Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt%, 70 wt%, and 8.55 wt%, 83 wt%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. Thein vitroandin vivoantitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.

[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].

OBJECTIVE: To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI). METHODS: The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed. RESULTS: In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent. CONCLUSION: For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.