Borcan Florin, Len Adel, Vlase Titus, Vlase Gabriela, Dudas Zoltan I, Popescu Roxana, Albulescu Ramona C, Dehelean Cristina A, Szuhanek Camelia A
Department I, Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy, Timisoara, 300041, Romania.
Budapest Neutron Centre, Institute for Energy Security and Environmental Safety, HUN-REN Centre for Energy Research, Budapest, 1121, Hungary.
Drug Des Devel Ther. 2025 Jul 8;19:5781-5799. doi: 10.2147/DDDT.S510803. eCollection 2025.
Nucleic acids are increasingly being recognized for their potential as therapeutic agents for the treatment of a variety of pathologies, such as genetic diseases, viral infections, and cancer. However, the safe delivery of these negatively charged macromolecules to their intended sites of action remains a major challenge.
This study aimed to design and characterize cationic particles for use as nonviral vectors for nucleic acid delivery; another primary objective was to evaluate the biocompatibility between the particles and DNA.
The particles were synthesized via a polyaddition process between isophorone diisocyanate and a mixture of polyethylene glycol and polycaprolactone diol. The structural characteristics were assayed using a variety of techniques, including measurements of pH, refractive index, and Zetasizer, drug release and penetration through an artificial membrane, SEM, FTIR and Raman spectroscopy, thermal analyses, cell viability, and in vivo evaluation of skin parameters.
The findings revealed that nearly neutral-pH particles were successfully synthesized, displaying a broad size distribution ranging from 400-900 nm, a prolonged release profile, and an encapsulation efficacy of 72.5%. Thermal analyses demonstrated that the samples remained stable at temperatures up to 200 °C, and the results of the spectroscopy, cell assay, and evaluations on mouse skin suggest that the obtained particles are safe for use as DNA carriers.
Cationic polyurethane carriers present a potential alternative to the more established polyethylenimine. However, additional studies are necessary to fully assess the therapeutic effectiveness of these formulations.
核酸作为治疗多种疾病（如遗传疾病、病毒感染和癌症）的治疗剂的潜力越来越受到认可。然而，将这些带负电荷的大分子安全递送至其预期作用部位仍然是一项重大挑战。
本研究旨在设计和表征用作核酸递送非病毒载体的阳离子颗粒；另一个主要目标是评估颗粒与DNA之间的生物相容性。
通过异佛尔酮二异氰酸酯与聚乙二醇和聚己内酯二醇的混合物之间的加成聚合反应合成颗粒。使用多种技术测定结构特征，包括pH、折射率和Zetasizer测量、药物释放和通过人工膜的渗透、扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）和拉曼光谱、热分析、细胞活力以及皮肤参数的体内评估。
研究结果表明成功合成了近中性pH的颗粒，其尺寸分布范围为400 - 900 nm，具有延长的释放曲线，包封率为72.5%。热分析表明样品在高达200°C的温度下保持稳定，光谱、细胞试验和对小鼠皮肤的评估结果表明所获得的颗粒作为DNA载体使用是安全的。
阳离子聚氨酯载体是更成熟的聚乙烯亚胺的潜在替代品。然而，需要进一步研究以全面评估这些制剂的治疗效果。
