葛根素-磷脂复合物及其纳米药物递送系统的构建与评估OA

[Objective]Puerarin,a medicinal substance derived from traditional Chinese medicine,has shown potential in cancer therapy in recent years and has been found to inhibit a variety of cancers.However,puerarin faces many challenges in practical applications,mainly including its low water solubility,poor transmembrane permeability,and rapid metabolism,which significantly limit its clinical effectiveness and application scope.Therefore,how to overcome these drawbacks and improve therapeutic efficacy of Pueraria Mirifica has become a pressing issue.The aim of this study is to develop an innovative oral nanodrug delivery system based on drug-phospholipid complex technology and trans-fluidic membrane emulsification to enhance the water solubility and trans-membrane permeability of puerarin,thereby prolonging the drug's duration of action in tumor tissues,and reducing its side effects.In addition,this paper aimed to evaluate the potential of this novel delivery system in improving anti-tumor metastatic effects,thus providing a safer and more effective drug delivery scheme for the clinical application of puerarin,and offering new therapeutic ideas for cancer treatment and prevention.[Methods]Puerarin-phospholipid complexes and oral nanodrug delivery systems based on puerarin-phospholipid complexes were prepared using drug-phospholipid complex technology and trans-fluidic membrane emulsification.The quality of the complexes and their nanoparticles,drug release behaviors,and anti-tumor metastatic abilities were systematically evaluated.[Results]The experimental results showed that the complex formed by puerarin and soy lecithin was not simply physically mixed,but was combined through weak interactions without forming new chemical bonds,which significantly improved the hydrophilicity of puerarin.This was confirmed by the results of scanning electron microscopy,X-ray diffraction,ultraviolet spectroscopy,infrared spectroscopy and nuclear magnetic resonance analysis.As observed by scanning and transmission electron microscopy,the puerarin-phospholipid complex nanoparticles showed a uniformly dispersed spherical structure with a particle size of about 80.8 nm.The lyophilized formulation of puerarin-soy lecithin complex nanoparticles obtained by freeze-drying exhibited an increased particle size of about 104.8 nm,with the surface potential still maintained at about-7 mV,and a drug loading capacity of 14.63％when employing mannitol as a lyophilization protectant.Ultraviolet spectroscopy tests showed that the lyophilized formulation had good long-term stability and the loss of drug loading was less than 10％when stored at 4 ℃ or room temperature for 3 months.In vitro drug release studies showed that the puerarin-phospholipid complex nano drug delivery system had a slow release effect compared to pure puerarin and was able to release the drug in tumor cells for a longer period.Further cellular experiments showed that the lyophilized formulation of puerarin-phospholipid complex nanoparticles was significantly more effective than pure puerarin in killing cells at the same concentration,suggesting that the complex significantly improved the transmembrane permeability of puerarin.The Transwell assay further confirmed that the nanodelivery system of puerarin-phospholipid complex was able to significantly inhibit the migration and invasion of tumor cells.[Conclusion]In this study,an oral nanodrug delivery system based on puerarin-phospholipid complexes was successfully prepared and its quality,drug release behavior and anti-tumor metastatic ability were systematically investigated.The drug-phospholipid complex technology significantly improved the transmembrane permeability of puerarin,enabling it to be taken up by cells more efficiently and thus enhancing the drug efficacy.The design of the nanoparticles enabled the slow release of puerarin and increased its accumulation in tumor cells,prolonging the duration of the drug's action and thus improving the antitumor effect.In addition,the puerarin-phospholipid complex nanodrug delivery system showed good biostability and low side effects,which makes it a great potential for clinical applications.In summary,the puerarin-phospholipid complex nanodrug delivery system not only provides a new solution for enhancing the efficacy of puerarin,but also opens up a more efficient and safer drug delivery pathway for the treatment and prevention of cancer,with broad application prospects.Future studies may further investigate the efficacy of this system in different cancer types and optimize its preparation process to promote its clinical translational application.