包裹血卟啉的PLGA微泡体内超声显影及其光毒性副反应考察

Detecting on ultrasound imaging in vivo and phototoxicity side-effect of hematoporphyrin-loaded PLGA microbubbles

目的:观察包裹声敏剂血卟啉的PLGA超声微泡造影剂兔肝体内超声显影效果并考察其光毒性副反应。方法:制备包裹声敏剂血卟啉的PLGA超声微泡造影剂(HP-PLGA),将该造影剂注入实验兔体内,观察造影剂对兔肝增强显影效果;另将35只Balb/c小鼠分为5组,分别将不同浓度的HP-PLGA超声微泡造影剂与单纯血卟啉溶液经尾静脉注入各组小鼠体内,阳光辐照后观察不同组小鼠的全身情况及背部皮肤表现,7天后取背部皮肤作HE染色比较观察光毒性副反应。结果:注入HP-PLGA超声微泡造影剂后,兔肝血管、实质回声均增强,持续时间超过20min。注射40mg/mL与20mg/mL血卟啉组小鼠背部皮肤出现明显的红斑焦痂,背部皮肤HE染色切片见表皮破坏,真皮及皮下组织中有炎性细胞浸润,而其他各组无明显反应。结论:HP-PLGA超声微泡造影剂体内超声显影效果较好,具备超声造影剂的基本特征。将声敏剂血卟啉包裹进高分子超声微泡造影剂内可以大大降低其光敏毒性副反应,为声动力学疗法提供了一种新的高效低毒的药物剂型。

Objective： To observe ultrasound imaging in vivo of rabbit liver and the phototoxicity of PIGA microbubble loaded hematoporphyrin （ HP - PLGA）. Methods： HP- PLGA microbubbles were prepared firstly, which were then injected into rabbit through tail vein to observe the ultrasound imaging in rabbit liver. In addition, 35 Balb/c mice were divided into 5 groups, then different concentration of HP- PLGA microbubbles and hematopolphyrin solution were injected into each group of mice; after 15 minutes of sun irradiation, general condition and the performance of the back skin of mice were observed, and the phototoxicity of back skin was detected by HE stain while there was no significant findings in the back skin of mice in other groups. Results： After injecting HP - PLGA microbubbles, the ultrasound image could be enhanced in rabbit liver blood vessels and liver parenchyma, and it could last longer than 20 minutes. In mice injected into hematoperphyrin of 40 mg/ml and 20 mg/ml, the skin of the back reacted by forming a large area of eschar, and epidermis damage and inflammatory cell infdtrated in dennis and subcutaneous tissue were seen in HE staining slice. Conclusion： HP- PLGA mierobubbles have basic characteristic of ultrasound contrast agent and HP- PLGA contrast agents could significantly reduce the phototoxieity side - effect of hematoporphyrin.