The Preparation Of Omniscan And Doctaxel Loaded Enzyme- Triggered Targeting Nanoparticles

In China, cancers become a major risk of death which is a serious threat to human lives. Each year, more than 20% of the total number of new cancer morbidity and mortality worldwide cases have occurred in China. Among them, the incidence of oral and maxillofacial malignant tumors ranked sixth in all cancers, and more than 30% of all kinds of oral and maxillofacial malignant tumors are tongue cancers which caused great damage to people’s health and life. Thus, for this patients, there is a compelling need for an effective therapy with a good imaging method to monitor the progress of treatment.Polyethylene glycol and Polycaprolactone are always used for preparation of drug carriers based on their remarkable biocompatibility. Via ring-opening copolymerization and double amidation reaction, we could synthesized Polycaprolactone and Polyethylene glycol with Peptide into mPEG-Pep-PCL copolymer, a new kind of enzyme target drug carrier. In some reports, this mPEG-Pep-PCL copolymer with Doctaxel loaded presented a better anti-cancer effects which could be used as a reliable carrier for chemotherapeutic drugs and imaging agents.[Objective] In this study, we used mPEG-Pep-PCL copolymer to load Omniscan and Doctaxel, and tested characterization of this nanoparticle.[Method] We inserted a gelatinase cleavable peptide (PVGLIG) between mPEG and PCL blocks, and then synthesized mPEG-Pep-PCL copolymer via ring-opening copolymerization and double amidation. Then, the Doctaxel and Omniscan loaded nanoparticles were prepared by double emulsion method. The appearance of NPs was observed by transmission electron microscopy (TEM). The real-time biodistribution of NPs was investigated by near-infrared fluorescent imaging.[Result] The diameter of NPs was 80.7±5.7nm, and in 13 days the NPs showed great stability. Observed by TEM, we found that the drugs in the nanoparticles. The drug loading content and encapsulation efficiency of Doctaxel was higher than Omniscan’s, the drug loading content of Doctaxel was 8.05%, the drug loading content of Omniscan was 44.60%; the encapsulation efficiency of Doctaxel was 44.27%, the encapsulation efficiency of Omniscan was 15.54%. The near-infrared fluorescent imaging showed that the NIR signals were observed in the tumor area, and the signals in the tumor was much higher than that in another organs.[Conclusion] It was feasible to load Doctaxel and Omniscan, one hydrophobic drug and one hydrophilic drug, together into the mPEG-Pep-PCL copolymer and formed stable nanoparticles which could target to tumor and stay in tumor area for at least 48h.