Docetaxel-loaded Poly Lactide-co-glycolide Nanoparticles For Non-small Cell Lung Cancer

ObjectiveLung cancer is the most common malignant tumor with morbidity and mortality worldwide,accounting for about 27% of all deaths.Docetaxel(DTX)is a complex taxane compound with significant inhibitory effects on various malignant tumors including lung cancer.However,docetaxel has poor water solubility and unstable absorption patterns in the body affect its clinical efficacy.Besides,DTX itself lacks specific targeting for tumor tissue,and the systemic toxicity of the drug itself needs to be improved.Therefore,it is urgent to develop a new DTX-based drug delivery system to improve the water solubility of drugs,improve the bioavailability of drugs,and improve the therapeutic effect of lung cancer.Compared with traditional free chemotherapeutic drugs,the nano-drug delivery system can not only improve the in vivo delivery of hydrophobic drugs,but also achieve long-term blood circulation of drugs through sustained release,and can also use Enhanced Permeability and Retention(EPR).Achieving passive targeting of tumors not only improves the bioavailability of the drug but also reduces the toxic effects of the drug itself on surrounding tissues.In this study,we designed a nano-delivery system based on poly lactide-co-glycolide(PLGA),which can efficiently transport docetaxel for the treatment of lung cancer.We constructed docetaxel-loaded nanoparticles and analyzed their physicochemical properties,stability,drug loading rate,and encapsulation efficiency,and compared the anti-tumor effects of docetaxel in the subcutaneous model of mouse lung cancer before and after encapsulation.Method1.Preparation and characterization of docetaxel nanoparticles.(1).Docetaxel-loaded nanoparticles are synthesized by double emulsion method.(2).The surface potential is measured by dynamic light scattering(DLS).(3).The internal structure of docetaxel-loaded nanoparticles was observed by transmission electron microscopy(TEM).(4).The entrapment rate and drug release of docetaxel were tested by UV spectrophotometer.(5).Detecting the docetaxel-loaded nanoparticles after incubation at different temperatures in PBS for different times,the temperature stability of the nanoparticles was examined by observing the change in the particle size distribution of the nanoparticles.2.Evaluation of anti-tumor effect in vitro and in vivo of docetaxel nanoparticles.(1).Using rhodamine B dye to simulate docetaxel,analyze the uptake of drugs by tumor cells after encapsulation(2).After treating the cells with docetaxel nanoparticles,the cell viability was determined by CCK-8 kit to determine the anti-tumor effect of docetaxel-loaded nanoparticles in vitro.(3).Evaluation of anti-tumor effects of docetaxel nanoparticles using subcutaneous xenografts of lung cancer in mice.(4).Evaluation of biosafety of docetaxel-loaded nanoparticles using normal mice ResultsThe docetaxel-loaded nanoparticles prepared in this study have a round shape and uniform size.The particle size is about 100 nm,and the hydrated particle size is about110 nm.It has a strong negative charge and is evenly dispersed.The nanosystem is more stable at low temperatures and has good drug loading capacity and sustained release capacity.Drug sustained release of docetaxel nanoparticles is p H sensitive.Under normal p H environment,the cumulative drug release of nanoparticles is only42.3% after 196 hours,while at low p H,the cumulative drug release can be as high as60%.The cellular uptake and cytotoxic cell assays of docetaxel nanoparticles confirmed that the drug can effectively enhance the uptake of cells after encapsulation,so it’s killing ability against tumor cells is significantly enhanced.Docetaxel-loaded nanoparticles exhibit significant anticancer effects in a mouse model of lung cancer and have a guiding significance for the clinical treatment of lung cancer.Besides,PLGA nanoparticles also have good biocompatibility,which not only can improve the anti-tumor effect of DTX,but also reduce the toxic side effects of the drug itself to some extent.ConclusionWe synthesized a biocompatible polymer nanoparticle to achieve efficient transport of docetaxel.This nanomedicine enhances the uptake of drugs by tumor cells and not only demonstrates excellent anti-tumor effects in vitro.At the same time,it shows good anti-tumor effect in the subcutaneous tumor model.The nano-system has good biosafety and lays a foundation for the effective transport and clinical application of docetaxel in the future.