Fabrication Of Serum Albumin Nanoparticles And Ultrasound-Regulated Drug Release

Smart Stimuli-Responsive Delivery,that is,when nanocarriers loaded with therapeutic drugs enter the tumor tissue,can release the drugs for tumor treatment under the tumor micro-internal environment or certain external specific stimuli.Albumin has been widely studied in drug delivery systems due to its excellent biocompatibility,biodegradability,high nutritional value and binding ability with multiple drugs.Ultrasound as a mechanical wave has the advantages of non-invasive,high controllability and high tissue penetration ability,so it is widely used in clinical diagnosis.In this paper,bovine serum albumin(BSA)nanoparticles were synthesized and used as a carrier for chemotherapeutic drugs.A new type of ultrasound-regulated drug delivery system was prepared,and its drug release ability under ultrasound and penetration in deep tissues were prepared.(1)We designed and prepared a nanoparticles BSA-ACVA-DOX which containing the anticancer drug Doxorubicin(DOX).BSA was used as the skeleton and ultrasonically cleavable4,4'-azobis(4-cyanovaleric acid)(ACVA)was used as the chemical cross-linking agent.The transmission electron microscopy and dynamic light scattering showed the prepared nanoparticles were uniformly distributed spherical,with a particle size of 171±2.8 nm and a Zeta potential of-19.8 mV.The DOX drug loading rate was 6.8%and the encapsulation rate was 94.5%.It has good stability in PBS buffer solution,and the particle size and polydispersity coefficient have not changed significantly within 7 days.It can quickly enter MCF-7 cells and localize in lysosomes within 30 min.It has good biocompatibility and the cell survival rate is more than 80%after incubation at 200 mg/L for 24 h.(2)1MHz,2.0 W/cm~2 was used as safe ultrasound conditions.And It was verified that the ultrasound conditions used in the experiment had no significant effects on biological macromolecules such as proteins,nucleic acids and enzymes.In vitro tests showed that the structure of BSA-ACVA-DOX nanoparticles was obviously destroyed under ultrasound stimulation(1.0 MHz,2.0 W/cm~2).The controlled"Off-On"release of drugs in the body can be achieved by exogenous ultrasound.The release rate can reach 16%within 30 s,and can be increased to 74%within 10 min.Ultrasound gives the system good tissue penetration ability.The DOX release rate is 35%under 1 cm tissue thickness in 3 minutes and 32%at 2 cm tissue thickness.Cytotoxicity experiments showed that the tumor cells can be effectively killed after3 min of ultrasound,and the cell survival rate is only 17%In summary,the albumin nanoparticles BSA-ACVA-DOX have good ultrasound-activated rapid drug release capabilities with high biosecurity and tissue permeability.It can controllable release drugs in space and time as a smart drug.The-ACVA-DOX NPs has a broad application prospects as a drug delivery system.