Construction and evaluation of puerarin-phospholipid complex and its nano drug delivery system

[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.

[研究目的] 葛根素（Puerarin）是一种源自中药的药用成分，近年来在癌症治疗中展现出应用潜力，且被证实可抑制多种癌症。然而，葛根素在实际应用中面临诸多挑战，主要包括水溶性低、跨膜通透性（transmembrane permeability）差以及代谢速度快，这些问题显著限制了其临床疗效与应用范围。因此，如何克服上述缺陷、提升葛根素的治疗功效已成为亟待解决的问题。本研究旨在基于药物-磷脂复合物技术（drug-phospholipid complex technology）与跨流体膜乳化法（trans-fluidic membrane emulsification）开发一种新型口服纳米药物递送系统，以改善葛根素的水溶性与跨膜通透性，从而延长药物在肿瘤组织中的作用时长并降低其毒副作用。此外，本研究旨在评估该新型递送系统改善抗肿瘤转移效应的潜力，从而为葛根素的临床应用提供更安全、高效的药物递送方案，并为癌症的治疗与预防提供全新的治疗思路。
[研究方法] 采用药物-磷脂复合物技术与跨流体膜乳化法，制备葛根素-磷脂复合物（puerarin-phospholipid complex）以及基于该复合物的口服纳米药物递送系统。对该复合物及其纳米粒的质量、药物释放行为以及抗肿瘤转移能力进行了系统性评价。
[研究结果] 实验结果表明，葛根素与大豆卵磷脂（soy lecithin）形成的复合物并非简单的物理混合，而是通过弱相互作用结合，未生成新的化学键，这显著提升了葛根素的亲水性。扫描电子显微镜、X射线衍射、紫外光谱、红外光谱以及核磁共振波谱分析结果证实了这一点。扫描与透射电子显微镜观察显示，葛根素-磷脂复合物纳米粒呈均匀分散的球形结构，粒径约为80.8 nm。以甘露醇（mannitol）作为冻干保护剂，通过冷冻干燥制备的葛根素-大豆卵磷脂复合物纳米粒冻干制剂，粒径增至约104.8 nm，表面电位仍维持在约-7 mV，载药量可达14.63%。紫外光谱测试结果表明，该冻干制剂具有良好的长期稳定性：在4℃或室温条件下储存3个月后，其载药量损失率低于10%。体外药物释放研究表明，与纯葛根素相比，葛根素-磷脂复合物纳米药物递送系统具有缓释效果，可在肿瘤细胞内更长时间地释放药物。进一步的细胞实验显示，在相同浓度下，葛根素-磷脂复合物纳米粒冻干制剂的细胞杀伤效果显著优于纯葛根素，表明该复合物显著提升了葛根素的跨膜通透性。Transwell实验（Transwell assay）进一步证实，葛根素-磷脂复合物纳米递送系统可显著抑制肿瘤细胞的迁移与侵袭能力。
[研究结论] 本研究成功制备了基于葛根素-磷脂复合物的口服纳米药物递送系统，并对其质量、药物释放行为以及抗肿瘤转移能力进行了系统性研究。药物-磷脂复合物技术显著提升了葛根素的跨膜通透性，使其更高效地被细胞摄取，从而增强了药物疗效。该纳米粒的设计实现了葛根素的缓释，并增加了其在肿瘤细胞内的蓄积，延长了药物作用时长，进而提升了抗肿瘤效果。此外，葛根素-磷脂复合物纳米药物递送系统展现出良好的生物稳定性与较低的毒副作用，具备良好的临床应用潜力。综上，葛根素-磷脂复合物纳米药物递送系统不仅为提升葛根素的疗效提供了全新解决方案，也为癌症的治疗与预防开辟了更高效、更安全的药物递送途径，具备广阔的应用前景。未来可进一步研究该系统在不同癌症类型中的疗效，并优化其制备工艺，以推动其临床转化应用。