Hybrid Bicelles For Hydrophobic Drug Delivery

According to statistics,more than 40% of drugs have poor water solubility,and the clinical application is greatly limited.While the nano-vectors have been developed to overcome the limitation.Recently,a nonspherical lipid vehicle called “bicelle” which was composed of long-chain phospholipid and either short-chain phospholipid or detergent has received comprehensive attention.As a biomembrane model,bicelles have been successfully applied in drug partitioning,structure membrane proteins and function of membrane associated proteins and drug delivery.Moreover,it was found that the nanoparticles in disc-like shape showed longer circulation time,more favorable cellular uptake and higher microvascular adhesion than in spherical shape.However,the poor stability affected its application of anticancer drug vector in vivo.Consequently,the organic-inorganic hybrid bicelles can significantly improve the stability of the bicelles and provide a greater possibility for its application in drug vector.In this study,the disc-like hybrid bicelle and cerasome with similar particle size and surface properties were prepared.And the difference of cellular uptake,adhesion and toxicity was detected.The results showed that there was no obvious difference in cell toxicity between the two kinds of vehicles.But the hybrid bicelles displayed faster and higher cellular adhesion and uptake.The results indicate that the disc-like hybrid bicelle has more advantages in drug delivery application than spherical cerasome.In order to study the drug carrier properties of hybrid bicelles,the hydrophobic doxorubicin(DOX)as a model drug and the drug loading performance,drug release behavior,safety and antitumor activity in vitro and in vivo of hybrid bicelles were discussed.It was found that the relatively higher drug-loading content(2.26%)and encapsulation efficiency(67.82%)was displayed at the ratio of 1:30(drug to lipid),and slower and p H sensitive release behavior in vitro.It also proved that it has excellent biosafety and effective antitumor activity in vitro and in vivo.Although the dense silica grid structure on the surface greatly improved the stability of hybrid bicelles,the negative effects of drug release was also produced.In order to improve the drug release behavior,different percentage of DSPE-PEG2000 was doped to control drug release.It was found that 57.38%,69.21%,78.69%,81.64% and 82.23% of hydrophobic doxorubicin was released within 120 h from the nanodiscs incorporating with 0%,2.5%,5%,10% and 20% DSPE-PEG2000.And the biosafety and antitumor activity were also evaluated.With the increase of DSPE-PEG2000 percentage,the drug release rate and release amount were improved greatly.And it showed good biosafety and higher antitumor activity in vitro and in vivo.To further develop the advantage of nano-vector and achieve a drug carrier with multiple functions,the indocyanine green(ICG)and DOX were encapsulated into hybrid bicelles which doped with 5% DSPE-PEG2000.The multiple hybrid bicelles realized photothermal therapy combined with chemotherapy and monitored by fluorescence imaging.The photostability of ICG was improved and the temperature was elevated under near infrared irradiation.The results also showed that compared to 37℃ the amount of released drug increased 20.91% at 42℃.In addition,the DOX/ICG@PEGHBs showed more accumulation on the tumor than free ICG.And the maximum accumulation amount was reached after injection of 12 h.The in vivo experiments prove that the NIR laser irradiation can effectively achieve photothermal therapy combined with chemotherapy.In summary,the hybrid bicelle can be applicated in hydrophobic drug carrier.And it had good biosafety and was able to realized effective antitumor therapy in vitro and in vivo.Also,the drug release behavior could be controlled by regulating the proportion of doped DSPE-PEG2000.Then the multifunctional hybrid bicelle which encapsulated with ICG and DOX can realize photothermal therapy combined with chemotherapy monitored by fluorescence imaging.