PDF(Pubmed)
Abstract：
UNASSIGNED: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains.
UNASSIGNED: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment.
UNASSIGNED: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum.
UNASSIGNED: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.
UNASSIGNED: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment.
UNASSIGNED: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum.
UNASSIGNED: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.
摘要：
■葡萄酒色斑是先天性毛细血管畸形的一种皮肤病。基于葡萄酒色斑的生物学特性和微针透皮给药的优势,我们打算构建一种与雷帕霉素（RPM）共同负载的纳米药物，一种抗血管生成药物,和光电氯(HPPH)，光敏剂，并将纳米药物与可溶解的微针（MN）整合，以实现针对葡萄酒色斑的抗血管生成和光动力联合治疗。
■首先，通过乳化溶剂挥发法制备了RPM和HPPH共负载纳米颗粒(RPM-HPPHNP),并研究了其在660nm激光照射下产生活性氧（ROS）的能力。小鼠血管内皮瘤内皮细胞(EOMA)用作研究对象。通过荧光显微镜和流式细胞术检查细胞摄取行为。通过MTT测定法(以游离RPM作为对照)检查在有或没有660nm激光照射的情况下RPM-HPPHNP对EOMA细胞的细胞毒性作用。然后，通过模塑方法将纳米药物与HA可溶性微针系统混合，获得了负载有RPM-HPPHNP（RPM-HPPHNP@HAMN）的透明质酸（HA）可溶性微针。通过扫描电子显微镜和电子万能试验机研究了RPM-HPPHNP@HAMN的形态特征和力学性能。通过锥虫蓝染色和H&E染色实验评价RPM-HPPHNP@HAMN对裸鼠皮肤的渗透能力。
■研究中制备的RPM-HPPHNP的粒径为150nm，在激光照射下产生大量ROS。在细胞层面,RPM-HPPHNP以时间依赖性方式被EOMA细胞吸收。在有或没有激光照射的情况下，RPM-HPPHNP的细胞毒性高于游离RPM。在激光照射下，RPM-HPPHNP具有更强的细胞毒作用,差异有统计学意义(P<0.05)。RPM-HPPHNP@HAMN的针尖高度为600µm，单针的机械性能为0.75048N。台盼蓝染色和HE染色表明，按压微针可在皮肤表面产生毛孔和穿透角质层。
■RPM-HPPHNP@HAMN可将RPM-HPPHNP经皮递送至病变组织，实现抗血管生成疗法和光动力疗法对葡萄酒色斑的协同治疗，为纳米载药微针给药系统的构建和临床治疗葡萄酒色斑提供了新的策略。
■首先，通过乳化溶剂挥发法制备了RPM和HPPH共负载纳米颗粒(RPM-HPPHNP),并研究了其在660nm激光照射下产生活性氧（ROS）的能力。小鼠血管内皮瘤内皮细胞(EOMA)用作研究对象。通过荧光显微镜和流式细胞术检查细胞摄取行为。通过MTT测定法(以游离RPM作为对照)检查在有或没有660nm激光照射的情况下RPM-HPPHNP对EOMA细胞的细胞毒性作用。然后，通过模塑方法将纳米药物与HA可溶性微针系统混合，获得了负载有RPM-HPPHNP（RPM-HPPHNP@HAMN）的透明质酸（HA）可溶性微针。通过扫描电子显微镜和电子万能试验机研究了RPM-HPPHNP@HAMN的形态特征和力学性能。通过锥虫蓝染色和H&E染色实验评价RPM-HPPHNP@HAMN对裸鼠皮肤的渗透能力。
■研究中制备的RPM-HPPHNP的粒径为150nm，在激光照射下产生大量ROS。在细胞层面,RPM-HPPHNP以时间依赖性方式被EOMA细胞吸收。在有或没有激光照射的情况下，RPM-HPPHNP的细胞毒性高于游离RPM。在激光照射下，RPM-HPPHNP具有更强的细胞毒作用,差异有统计学意义(P<0.05)。RPM-HPPHNP@HAMN的针尖高度为600µm，单针的机械性能为0.75048N。台盼蓝染色和HE染色表明，按压微针可在皮肤表面产生毛孔和穿透角质层。
■RPM-HPPHNP@HAMN可将RPM-HPPHNP经皮递送至病变组织，实现抗血管生成疗法和光动力疗法对葡萄酒色斑的协同治疗，为纳米载药微针给药系统的构建和临床治疗葡萄酒色斑提供了新的策略。
