Study On Gelatin Peptide As A Carrier Of Nano Formulations Of Paclitaxel

Taxol(Paclitaxel,PTX),derived from a natural plant called yew(Taxus bre-vifolia Nutt),is an anti-cancer drug,which mainly used to treat breast cancer,ovarian cancer,non-small cell lung cancer,head and neck cancer,melanoma and some other diseases in the clinical application.Because of its unique action mechanism,totally new source,and good clinical efficacy,PTX is usually considered to be one of the best broad-spectrum anti-cancer drugs,but it has a lower solubility(only 0.006 mg / mL in water).Human albumin-bound paclitaxel(Abraxane?)nanoparticle which paclitaxel was loaded by human albumin(HAS)improved the solubility and bioavailability of PTX,yet the limited resource and high costs of HAS are the new problems.Therefore,gelatin peptide nanoparticles,with properties of biodegradable,reliable,non-immunogenic,and rich resource,were design to be a new carrier to replace HAS in this work.Objective: Preparation novel Nanoparticle Gelatin Bound Paclitaxel(ngb-PTX)and its freeze-dried powders,which paclitaxel was as raw materials and gelatin peptide was as a carrier,and then some of the physiological properties were tested.Furthermore,in vivo pharmacokinetics were carried out to evaluate the feasibility in chemotherapy of ngb-PTX.Method: High-pressure homogenization method was used to prepared ngb-PTX,which was lyophilized to preserve.The optimal formulation and homogeneous conditions were obtained through single factor experiments,the nanoparticles size,dispersion,and ? potential were tested by using a laser scattering particle size and ? potential detector,and transmission electron microscopy and scanning electron microscopy were utilized to observe the microstructure of nanoparticles.The crystal characteristics of ngb-PTX was revealed by X-ray diffraction instrument,the encapsulation efficiency and the level of loading drug were detected by HPLC,and thermostat shaker method was used to determine the level of drug release in vitro.the drug-time curve of ngb-PTX were obtained by HPLC detection and the animal model of SD rats,the compartment models,the peak time,AUC,T1/2,and other indicators were analyzed by DAS.2.0 with the control of commercial Paclitaxel Injection and Abraxane?.Results: The initial ngb-PTX emulsion formulation was obtained,which the chloroform containing PTX was as an oil phase,and gelatin peptide solution was as aqueous phase,and then the water and chloroform were removed by freeze-dried method.The optimal conditions of ngb-PTX emulsion from single factor were as followed: pH 6.5,the ratio of oil phase to aqueous phase was 3:100(v/v),the ratio of PTX to gelatin peptide was 1:20(g/g),the concentration of PTX was 1 mg/ml,the homogenization pressure was 1200 bar with and 10 cycles.In addition,the optimal conditions for the preparation of ngb-PTX freeze-dried powder were as followed:-80 ? frozen for 4 h,lyophilized for 48 h,and finally keep to 20 ?.when the ngb-PTX frozen-dried powder was reconstituted,slow and adherent addition saline followed by standing for 10 min was needed.The suspension,before and after frozen-dried,was blue opaline transparent,particle size was less than 200 nm,distribution coefficient was less than 0.25,? potential was-27.89 ± 1 mV,and the stability was more than 24 h.TEM revealed that nanoparticle surface was rough and spherical.Furthermore,SEM showed that the nanoparticles was the disk shape.The HPLC data expressed that the average entrapment efficiency of ngb-PTX was 50.59 ± 6.53%,the level of average loading drug was 2.65 ± 5.16%(n = 3),the release mode in vitro was released slowly,with an equation(ln(1-Q)=-0.1050t-0.4214,r = 0.9774).The pharmacokinetic results illustrated that the concentration-time curve of ngb-PTX was Two Lever Model,t1/2? was 0.95 min,t1/2? was 25.84 min,CL and AUC(0-?)were 0.061 and 205.77 L/min/kg,respectively,and the PTX was completely released within 1h.Conclusion: The ngb-PTX prepared by high pressure homogenization possessed the features of narrow particle size distribution,stable potential,high stability with no obvious changes before and after frozen dry.ngb-PTX can greatly improve the solubility of the drugs,in vitro release slowly,The pharmacokinetic results showed that the basic parameters were significantly different from that of the listed drug,Under the same dose of ngb-PTX,Under the same dose,the elimination rate of ngb-PTX is fast,AUC(0-?)less than the other two drug formulations,The later to be further explore ngb-PTX tissue distribution and anti-tumor activity and toxicity and plasma concentration,provide the basis for the further development of drugs.Therefore,it is feasible that gelatin peptide was as paclitaxel nanoparticles carrier,which worth great further research and broad market prospects.