Synthesis Of Amphiphilic Hydroxypropyl-?-Cyclodextrin And It Paclitaxel-loaded Micelles

At present,maglignant tumors have become the first category of "killers" that affect the health and safety of human life.Cancer is also one of the most serious problems in public health worldwide.The diversity,complexity and heterogeneity of tumors have affected the efficiency of cancer treatment to some extent.Today,the earlier prediction,detection and treatment of cancer is the biggest challenge facing humans in a cancer-free world.Traditional therapy,light therapy and synergistic therapy are the clinical treatments for cancer.Chemotherapy is still the main clinical strategy for most malignant tumors.However,traditional small molecule anticancer drugs have many undesirable properies such as low solubility,low bioavailability and poor targeting.These have affected the use of drugs in chemotherapy.With the wide application of nanotechnology,drug delivery systems are moving towards high efficiency,targeting and intelligence.The development and utilization of drug delivery system for nanoparticles has shown good prospects.In the past twenty years,drug-loaded micelles have been shown to be one of the ways to improve the molecular poor properties of anticancer drugs.Cyclodextrin is non-toxic and biodegradable.It has been approved by the U.S.Food and Drug Administration(FDA)as a pharmaceutical excipient.Partial cyclodextrins has been used to improve the solubility of the drug due to its special spatial configuration.Therefore,micelles are formed by chemical bond chains on the basic skeleton of cyclodextrin.Micellar loaded paclitaxel(PTX)was used to improve the solubility,bioavailability and dissolution properties of the drug.The research contents of this article are as follows:(1)Synthesis and characterization of amphiphilic cyclodextrin derivatives.Lauric acid(LA)and hydroxypropyl-?-cyclodextrin(HP-?-CD)were used as raw materials to synthesize the amphiphilic cyclodextrin micelle carrier.The hydrophobic chain segment in the carrier were lauric acid.The hydrophilic chain segment in the carrier were hydroxyl groups in HP-?-CD.The corresponding characteristic adsorption peaks of LA-HP-?-CD were detected by infrared spectrum and nuclear magnetic resonance spectrum.The average degree of substitution of the product was 0.30 and the relative molecular mass was 1599.4 g/mol.(2)Preparation of PTX/LA-HP-?-CD drug-loaded micelles.The standard curve of paclitaxel was drawn by HPLC.The curve was Y=18091926.28X-4819.32,R2=0.9999.The critical micelle concentration of LA-HP-?-CD was determined to be 0.075 mg/mL by pyrene as fluorescent probe.The effects of single factor test and orthogonal test on escapsulation rate and drug loading were investigated synthetically.The optimum preparation conditions of drug-loaded micelles were determined by experiments.The carrier concentration was 2.5 mg/mL.The ratio of carrier to the drug was 10:3.5.The ultrasonic time was 1.5 min.The ultrasonic power was 270 W.The average encapsulation rate was 75.62%.The average charge was 20.93%.(3)Physicochemical properties of PTX/LA-HP-?-CD and its release in vitro and in vivo.The average particle size and Zeta potential of PTX/LA-HP-?-CD micelles were determined by dynamic light scattering.The average particle size was(237.20±10.32)nm.The Zeta potential was(-18.37±2.76)mV.The spherical morphology of the drug-loaded micelles was determined by scanning electron microscope.FT-IR,SEM,XRD,TG and DSC were used to analyze the products and verify the formation of the micelles.In the simulated human stomach and intestinal environment,the saturated solubility of PTX/LA-HP-?-CD was 39.76 ?g/mL and 55.42?g/mL.The values were 3.80 times and 4.15 times higher than PTX.The accumulative release of the drug loading micelles was 57.90%and 78.59%at 720min.The values were 2.39 times and 2.35 times higher than PTX.The MTT method was used to explore the inhibition of PTX/LA-HP-?-CD.The inhibitory effect of drug-loaded micelles on cells was always higher than that of PTX.The IC50 was 0.40 ?g/mL.The curve of blood concentration of PTX/LA-HP-?-CD with time was investigated by gavage in rats.The Cmax of the drug-loaded micelles was 300.420 ng/mL.The Tmax was 0.417 h.The AUC(0-t)was 656.934 ng/mL*h.Therefore,PTX/LA-HP-?-CD drug-loaded micelles can significantly increase the solubility of PTX.It can also improve the drug dissolution rate and bioavailability.This substance will become a potential for clinical application of a new oral pharmaceutical preparation.