Preparation And Properties Of FFC/JAP Based Nano Micellar Delivery System

In order to develop a novel polymeric nanomicelle drug delivery system with Jerusalem artichoke polysaccharide（JAP）as the hydrophilic group,JAP-based drug-loaded nanomicelle system（FFC/JAP-SA,FFC/JAP-HA）was prepared by chemical modification/ultrasound/molecular self-assembly method,and its structure,particle size,potential,and surface morphology were characterized with fourier transform infrared spectroscopy（FT-IR）,nuclear magnetic resonance（NMR）,thermogravimetry（TG）,dynamic light scattering（DLS）,scanning electron microscope（SEM）,and transmission electron microscope（TEM）.Meanwhile,the preparation process of drug-loaded micelle was optimized by the response surface method with encapsulation efficiency as the evaluation indexe.The critical micelle concentration（CMC）,biocompatibility,antibacterial properties,in vivo and in vitro release characteristics,and pharmacokinetic characteristics were evaluated separately by pyrene fluorescence spectroscopy,hemolysis test,cytotoxicity test,antibacterial test,in vitro release test,and stability test.The results showed that JAP was connected with stearic acid（SA）and hyaluronic acid by an ester bond.The particle sizes of JAP-SA and JAP-HA were 202.10±3.40 nm and 179.10±1.86 nm,respectively,and the appearance of blank nanomicelles was spherical,and the surface was smooth and full;the particle sizes of FFC/JAP-SA and FFC/JAP-HA were 321.20±2.50 nm and 329.80±2.30 nm,but the surface of drug-loaded nanomicelles was wrinkled and not smooth.The pyrene fluorescence spectroscopy results showed that the CMC of JAP-SA and JAP-HA was 8.10×10^-3mg/m L and 3.30×10^-2mg/m L,indicating that it had strong dilution stability.The optimal preparation condition of FFC/JAP-SA optimized by response surface method was as follows:the drug loading ratio was 0.59,the reaction time was 4.54 h,the dialysis time was 26.88 h,as the results of that the encapsulation rate of the prepared micelle was（44.20±2.04）%;similarly,Design Expert 8.0 software analysis,using encapsulation rate as evaluation index,obtained the optimal preparation process of FFC/JAP-HA when the drug load ratio was 0.93,the reaction time was 6.4 h,and the dialysis time was 30.48 h.The encapsulation rate could reach（37.98±0.53）%.The two drug-loaded nanomicelles showed good in vitro drug release performance in different p H releasing media of PBS or HCl,and the release mode was consistent with the Weibull model.Furthermore,the results of the antibacterial test,hemolysis test,and cytotoxicity test suggested that the drug-loaded nanomicelles had good antibacterial activity and biocompatibility.Pharmacokinetic results suggested that,compared with florfenicol（FFC）in vivo,the area under the plasma concentration-time curve（AUC）of the drug-loaded micelle was significantly increased（P<0.01）,and the half-life reached 708.33±15.90 min;the half-life(T_1/2)of FFC/JAP-HA group was 679.34±23.20 min,and the under the blood concentration curve（AUC）was 1001.64±19.70 min,indicating that the drug-loaded nanomicelles could delay the elimination of FFC in rats.The results of the stability test demonstrated that when the drug-loaded nanomicelles were stored at 20°C for 6 months,the entrapment efficiency did not change significantly,indicating good storage stability,which laid a foundation for the development of a new polymeric nanomicelle drug loading system with JAP as a hydrophilic group.