Study Of Paclitaxel Albumin Nanoparticles

Paclitaxel?PTX?is a broad-spectrum anti-tumor dr?g that breaks the dynamic balance between microtubules and tubulin dimers by binding to free tub?Lin,thereby inhibiting cell division and proliferation,playing a role of anti-tumor.The available formulations in market are solvent-borne paclitaxel injection?Taxol?and albumin-binding paclitaxel injection?Abraxane?.Taxol may cause acute allergic reactions because of polyoxyethylene castor oil,which need to prevent by glucocorticoid before using.With human serum albumin as carrier,Abraxane has the advantages of non-toxic,non-immunogenicity,biodegradable and good biocompatibility.Albumin nanoparticles are commonly prepared by desolvation method,emulsification curing method,pH-coacervation method and nab-technology.Methanol,dichloromethane and other organic solvents are usually needed to be added,which might exist the problem of chemical toxicity and the preparation process being complicated and so on.In order to solve the above problems,a new method,liquid adsorption drug loading method,was proposed in this paper for the preparation of paclitaxel human serum albumin nanoparticles?PTX-HSA-NPs?.In this method,paclitaxel was dissolved in ethanol,then low-weight polyethylene glycol?l-PEG?was added and ethanol was removed by rotary evaporation to form l-PEG-PTX complex.The complex was mixed with human serum albumin powder and added to phosphate buffer?PBS?to form nanoparticles under ultrasound.In the process of preparation,the ethanol was removed by rotary evaporation and dialysis.The problem of organic solvent residue was solved,and the preparation process was simple.The method provided a new idea for preparation of PTX-HSA-NPs.Now,this method has been applied for patent that the the patent application number is 201710290102.5.Through the investigation of PEG,paclitaxel,albumin,ethanol,dispersing solvent and ultrasonic power,the optimal prescription was obtained.Self-made PTX-HSA-NPs and the Abraxane were both spherical.Their particle size were 135.9±1.6nm and 146.2±1.1nm,Zeta potential were-32.9±0.9mV and-26.4±1.2mV,drug loading were 10.03±0.44%and9.72±0.09%and entrapment rate were 99.98±0.01%and 99.83±0.03%.All of these indicated that the physical states was no difference in Abraxane and Self-made PTX-HSA-NPs.Self-made PTX-HSA-NPs were released for more than 100 hours in vitro,indicating its sustained release effect.The res?Lts of stability analyzer showed that there was no aggregation,precipitation and flocculation of self-made PTX-HSA-NPs and Abraxane suspensions in 48 h,and the physical stability was good.X-ray powder diffraction?XRD?and differential scanning calorimetry?DSC?showed that PTX existed in an amorphous state both for the self-made PTX-HSA-NPs and Abraxane.Circular dichroism?CD?showed that there was no significant change in HSA secondary structure before and after drug loading.The pharmacokinetic experiments showed that T_1/2?of self-made PTX-HSA-NPs,Abraxane and Taxol were 0.40±0.02?0.55±0.23 and0.28±0.08h,T_1/2?were 5.28±0.0.63?5.92±1.60 and 2.60±0.11h,T_1/2?were0.04±0.003?0.06±0.03 and 0.18±0.06h,AUC were 1.97±0.32?2.19±0.24 and5.55±0.09?g·h/mL?CL were 0.0032±0.0004?0.0013±0.00002 and0.0036±0.0006 mg/kg/h/?ng/mL?.Tissue distribution showed that Taxol was more distributed in liver,and the concentrations of PTX of PTX-HSA-NPs and Abraxane in tumor tissues were significantly higher than Taxol.In the pharmacodynamics experiment,the inhibitory rates of self-made PTX-HSA-NPs and Abraxane high,middle and low dose groups were higher than Taxol.The above experiments show that self-made PTX-HSA-NPs and Abraxane both changed the pharmacokinetic behavior of PTX,compared with Taxol,enhanced the targeting of dr?gs in vivo,and improve the efficacy of dr?gs in a certain extent.The preparation of PTX-HSA-NPs by liquid adsorption dr?g loading method is a new attempt.Compared with the traditional preparation methods,this method solves the problem of organic solvent residues and the preparation process is simple.In vitro and in vivo experiments show the feasibility of this preparation method.