Guo Xueqin, Xia Tian, Wang Huan, Chen Fang, Cheng Rong, Luo Xiaoming, Li Xiaohong
Key Laboratory of Advanced Technologies of Materials Ministry of Education of China School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
Pharm Res. 2014 Apr;31(4):874-86. doi: 10.1007/s11095-013-1209-y. Epub 2013 Sep 25.
The lack of control over microvasculature formation remains a key roadblock to the therapeutic vascularization and regeneration of functional tissues. In the current study, the integration of plasmid DNA (pDNA) condensation and electrospraying technologies was proposed to promote the regeneration of mature blood vessels through injectable or infusible administration of microparticles.
Calcium phosphate (CP) nanoparticles with encapsulated plasmids encoding vascular endothelial growth factors (pVEGF) and basic fibroblast growth factor (pbFGF) were synthesized using reverse microemulsions. Electrosprayed microparticles with the loading of CP-pDNA nanoparticles were evaluated on both endothelial cells and smooth muscle cells and after subcutaneous infusion into animals.
CP-pDNA nanoparticles was obtained with an average size of around 110 nm and electrosprayed into microparticles, resulting in high loading efficiency and extended protection on pDNA from external DNase environment. The inoculation of poly(ethylene glycol) into microparticle matrices realized a gradual release for 4 weeks of CP-pDNA nanoparticles, leading to an incremental transfection efficiency and strong secretion of extracellular matrices. After subcutaneous infusion of microparticles with encapsulated both CP-pVEGF and CP-pbFGF nanoparticles, significantly higher densities of blood vessels were achieved than those containing individual nanoparticles, and induced a rapid generation of mature blood vessels with few cytotoxicity and inflammation reactions.
Electrosprayed microparticle with CP-pDNA nanoparticles encapsulated promoted the formation of vascular networks, providing clinical relevance for therapeutic vascularization and regeneration of functional tissues after injection to ischemic sites or entrapment into tissue engineering scaffolds.
对微血管形成缺乏控制仍然是功能性组织治疗性血管化和再生的关键障碍。在本研究中，提出将质粒DNA（pDNA）凝聚和电喷雾技术相结合，通过可注射或可输注的微粒给药来促进成熟血管的再生。
使用反向微乳液合成包裹编码血管内皮生长因子（pVEGF）和碱性成纤维细胞生长因子（pbFGF）质粒的磷酸钙（CP）纳米颗粒。对负载CP-pDNA纳米颗粒的电喷雾微粒在内皮细胞和平滑肌细胞上以及皮下注入动物后进行评估。
获得了平均尺寸约为110nm的CP-pDNA纳米颗粒，并将其电喷雾成微粒，从而实现了高负载效率，并对pDNA在外部DNase环境中提供了延长的保护。将聚乙二醇接种到微粒基质中实现了CP-pDNA纳米颗粒4周的缓释，导致转染效率逐渐提高和细胞外基质的强烈分泌。皮下注入同时包裹CP-pVEGF和CP-pbFGF纳米颗粒的微粒后，实现的血管密度显著高于含有单个纳米颗粒的情况，并诱导了成熟血管的快速生成，且细胞毒性和炎症反应较少。
包裹CP-pDNA纳米颗粒的电喷雾微粒促进了血管网络的形成，为注射到缺血部位或包埋到组织工程支架后功能性组织的治疗性血管化和再生提供了临床相关性。
