Preparation and characterization of an ultrasound-controlled polypeptide nanoparticle drug release system
ZHANG Yu 1, 2, YIN Hao 2, WANG Qinyang 1, 2.
1.Department of Tumor Chemoradiotherapy, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325035, China;
2.Institute for Advanced Research, Wenzhou Medical University, Wenzhou 325035, China
ZHANG Yu,YIN Hao,WANG Qinyang.. Preparation and characterization of an ultrasound-controlled polypeptide nanoparticle drug release system[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(7): 565-573.
Abstract：Objective: To design and prepare an ultrasound-controlled polypeptide nanoparticle drug release system, and to characterize its drug inclusion rate and release rate after ultrasound. Methods: By adding 5K, 10K and 20K polyethylene glycol amine initiators and polypeptides with polymerization degree 20, polymerization degree 30 and polymerization degree 40, respectively, eight different types of polypeptide nanoparticle drug release systems were synthesized, including 5K initiator polymerization degree of 20[5K(1:20)], 5K(1:30), 5K(1:40), 10K(1:20), 10K(1:30), 10K(1:40), 20K(1:30) and 20K(1:40). Considering that the side chain of polypeptide can be modified, ultrasound sensitized agent was added, and the modification of ultrasound sensitized agent on polypeptide was characterized by means of UV-visible light. Firefly luciferase has a specific response to ATP, so it can characterize the ATP-coated polypeptide nanoparticle drug release system with ultrasound control, including the inclusion rate, particle size after inclusion, ultrasound particle size change and the release rate of ultrasound response. In addition, the effect of different ultrasound power and ultrasound time on ATP release rate were analyzed. Results: Of 8 kinds of ultrasound-controlled polypeptide nanoparticle drug release systems, the one with 5K(1:40) was insoluble, while the other 7 kinds confirmed the modification of ultrasound sensitized agent through UV-visible light, with good solubility, all of which could realize the inclusion of ATP. In addition, all of them were ultrasound responsive with varying degrees of particle size reduction and ATP release after ultrasound. Among them, the one with 10K initiator polymerization degree of 30 after ultrasound had the highest ATP release rate of 15%, showing statistical difference compared with the ones with 5K(1:20), 5K(1:30), 10K(1:20), 10K (1:40), 20K(1:30) and 20K(1:40). The polypeptide nanoparticle drug release system with 10K(1:30) had good drug loading stability. Without ultrasound treatment, there was no significant difference in ATP content and particle size within 24 hours compared with 0 hour. The polypeptide nanoparticle drug release system with 10K(1:30) was influenced by ultrasound power and ultrasound time. Under the same ultrasound time, the ATP release rate gradually increased with the ultrasound power. There was statistical difference between the 1.0 Wcm-2 group and the 0.5 Wcm-2 group, between the 1.5 Wcm-2 group and the 1.0 Wcm-2 group, between theb 2.5 Wcm-2 group and the 2.0 Wcm-2 group. However, cell viability gradually decreased with the ultrasound power, with statistical difference between the 1.5 Wcm-2 group and the 1.0 Wcm-2 group, between the 2.0 Wcm-2 group and the 1.5 Wcm-2 group, between the 2.5 Wcm-2 group and the 2.0 Wcm-2 group. Under the same ultrasound power, the ATP release rate of the polypeptide nanoparticle drug release system also increased gradually with the ultrasound time, showing statistical difference between the 10 min group and the 1 to 8 min group. Conclusion: The results of a series of screening experiments showed that the ultrasound-controlled polypeptide nanoparticle drug release system with 10K(1:30) has the best ultrasonic response, with 23% inclusion rate and a particle size of 129 nm. The particle size changes by 10 nm after ultrasound, and the ultrasound-controlled release efficiency can reach 15%. When the ultrasound power is 1.0 Wcm-2 and the ultrasound time is 10 min, it has good drug release efficiency and better safety with minimal cell damage.
