Preparation And Properties Of The Brefeldin A Solid Lipid Nanoparticles

LNPs have attracted much attention in the pharmaceutical industry and have broad development prospects as a variety of therapeutic agent carriers.SLN is a kind of lipid nanoparticles.It is a new nano drug delivery system that is developing rapidly in recent years.It can enhance drug stability and targeting,reduce adverse drug reactions,prolong drug half-life and increase drug bioavailability.BFA has a variety of biological activities,such as antifungal,antiviral,nematode and mitotic,but it can’t be widely used in clinical treatment because of its poor water solubility,short half-life and poor bioavailability.Based on this,this paper mainly explored the preparation,characterization and antitumor activity in vitro of multifunctional BFA-SLNs.（1）BFA-SLNs were prepared by ultrasonic dispersion method.Through the investigation of preparation process and single factor,determing the factors and level of orthogonal test,and the best formulation process and ratio were determined.The physical and chemical properties of BFA-SLNs were determined.The results showed that,the appearance of BFA-SLNs was spherical,the average particle size was（185.38±4.74）nm,the dispersion was great,the zeta potential was（-66.10±2.26）m V.The entrapment efficiency was more than 80%,the stability was perfect and it showed good sustained-release effect.In vitro antitumor activity test,the survival rate of human hepatoma Hep G2 cells treated with BFA-SLNs at high concentration was significantly lower than that of free BFA,and the antitumor activity was significantly enhanced.（2）Based on the previous formulation and process,5%folate targeted fragments were added to prepare folate targeted SLNs（FA-BFA-SLNs）.The characterization results showed that after the addition of targeted fragments,the appearance,average particle size,zeta potential and entrapment efficiency hadn’t significant changes,and the sustained-release effect was enhanced.In vitro antitumor activity test,FA-BFA-SLNs at various concentrations had stronger inhibitory effect on the proliferation of human hepatoma Hep G2cells and significantly lower cell survival rate than ordinary BFA-SLNs.（3）Fullerene C₇₀ and tetraethylene glycol（TEG）were self-assembled to form water-soluble fullerene nanoparticles(C₇₀-TEGs),and then we used theπ-πstacking of fullerene C₇₀ nanoparticles SP² hybrid carbon atoms and docetaxel（DTX）benzene ring to achieve efficient loading and prepare water-soluble fullerene drug loaded nanoparticles(DTX/C₇₀-TEGs).BFA and DTX/C₇₀-TEGs were co encapsulated in SLN(BFA-DTX/C₇₀-TEGs-SLNs)by film dispersion-emulsification method.The best formula was determined by orthogonal test.The physical and chemical properties were determined.The results showed that the appearance of BFA-DTX/C₇₀-TEGs-SLNs was spherical,there was no adhesion,the particle size was normally distributed between 300 nm～400 nm,and the stability was great.The cumulative release experiment in vitro showed that BFA was slowly released within 72 hours and DTX began to release at 6 hours,reaching a dual sustained-release effect.The study of antitumor activity in vitro showed that BFA-DTX/C₇₀-TEGs-SLNs achieved synergistic administration and significantly enhanced antitumor activity.In the biological imaging experiment of tumor cells,the signal of fullerene nanoparticles could be obviously detected,which could clearly reflect the growth state of cells.