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负载粒细胞集落刺激因子的脂质体的制备及体外特性:生殖医学的未来展望

Formulation and In Vitro Characterization of Granulocyte-Colony-Stimulating-Factor-Loaded Liposomes: Future Prospective in Reproductive Medicine.

作者信息

Obedkova Kseniia V, Khalenko Vladislava V, Tovpeko Dmitry V, Ryzhov Julian R, Bespalova Olesya N, Tapilskaya Natalya I

机构信息

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, Russia.

出版信息

Int J Mol Sci. 2025 Mar 17;26(6):2689. doi: 10.3390/ijms26062689.

Abstract

Drug delivery systems enhance drug efficacy while minimizing side effects. Liposomes, as well-studied and clinically approved carriers, offer biodegradability, biocompatibility, and low toxicity, making them suitable for delivering various pharmacological agents. Granulocyte colony-stimulating factor (G-CSF), a key growth factor, has shown therapeutic potential, particularly in infertility treatment. It effectively manages chronic and refractory endometritis by improving endometrial receptivity and increasing embryo implantation success. Studies indicate that G-CSF promotes endometrial growth and enhances the uterine microenvironment, benefiting patients with recurrent implantation failures and chronic endometritis. Encapsulation of G-CSF in liposomes enhances its stability, bioavailability, and controlled release. G-CSF-loaded liposomes were prepared using passive loading via the thin-film hydration method. The size of the liposomes, polydispersity index (PDI), and zeta potential were determined using dynamic and electrophoretic light scattering methods, and the encapsulation efficiency was measured using high-performance liquid chromatography. The morphology of the liposomes was established and confirmed using cryogenic transmission electron microscopy. The cytocompatibility of the G-CSF-loaded liposomes was evaluated on human dermal fibroblasts using an MTT assay. The G-CSF-loaded liposomes had an average particle size of 161.9 ± 9.9 nm, a PDI of 0.261 ± 0.03, and a zeta potential of +2.09 ± 0.10 mV, exhibiting high physical stability during long-term storage at +4 °C and 60% humidity. The passive loading method resulted in a 52.37 ± 3.64% encapsulation efficiency of the active substance. The analysis of cell viability revealed no cytotoxicity toward liposomes loaded with G-CSF and demonstrated a dose-dependent effect on the viability of human dermal fibroblasts. Thus, the obtained data confirm the successful preparation of G-CSF-loaded liposomes. However, to fully understand their effectiveness in biomedical applications, further research is needed, including an evaluation of their effectiveness in vivo. Such studies will help in determining the potential of these formulations for specific biomedical purposes and evaluating their safety and efficacy in living systems.

摘要

药物递送系统可提高药物疗效,同时将副作用降至最低。脂质体作为经过充分研究且已获临床批准的载体,具有生物可降解性、生物相容性和低毒性,使其适用于递送各种药物制剂。粒细胞集落刺激因子(G-CSF)是一种关键生长因子,已显示出治疗潜力,尤其是在不孕症治疗方面。它通过改善子宫内膜容受性和提高胚胎着床成功率,有效治疗慢性和难治性子宫内膜炎。研究表明,G-CSF可促进子宫内膜生长并改善子宫微环境,对反复着床失败和慢性子宫内膜炎患者有益。将G-CSF包裹在脂质体中可提高其稳定性、生物利用度和控释性。采用薄膜水化法通过被动载药制备了载G-CSF脂质体。使用动态和电泳光散射法测定脂质体的大小、多分散指数(PDI)和zeta电位,并使用高效液相色谱法测量包封率。使用低温透射电子显微镜确定并确认了脂质体的形态。使用MTT法在人皮肤成纤维细胞上评估了载G-CSF脂质体的细胞相容性。载G-CSF脂质体的平均粒径为161.9±9.9nm,PDI为0.261±0.03,zeta电位为+2.09±0.10mV,在+4℃和60%湿度下长期储存期间表现出高物理稳定性。被动载药法使活性物质的包封率达到52.37±3.64%。细胞活力分析显示,载G-CSF脂质体对人皮肤成纤维细胞无细胞毒性,并对其活力表现出剂量依赖性效应。因此,所获得的数据证实了载G-CSF脂质体的成功制备。然而,为了全面了解它们在生物医学应用中的有效性,还需要进一步研究,包括评估它们在体内的有效性。此类研究将有助于确定这些制剂在特定生物医学目的方面的潜力,并评估它们在活体系统中的安全性和有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c9/11943289/43d2d29e40dd/ijms-26-02689-g001.jpg

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