Fiberoptic Microneedle Device Facilitates Volumetric Infusate Dispersion During Convection-Enhanced Delivery in the Brain
Fiberoptic Microneedle Device Facilitates Volumetric Infusate Dispersion During Convection-Enhanced Delivery in the Brain
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DOI：
10.1002/lsm.22156
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发表时间：
2013-09-01
影响因子：
2.4
通讯作者：
Rossmeisl, John H., Jr.
中科院分区：
文献类型：
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作者：
Hood, R. Lyle;Andriani, Rudy T., Jr.;Rossmeisl, John H., Jr.
背景和目的设计并制造了一种光纤微针装置(FMD)，旨在通过对流增强输送(CED)同时输送亚致死剂量的光热来增强大分子在脑内的体积扩散。本研究的目的是通过在活体啮齿动物模型中展示1064 nm激光能量的共传递增强流体示踪剂分子的分散。材料和方法制备了能够通过单个光导毛细管共同传递流体和激光能量的FMD。将16只麻醉大鼠双侧大脑半球立体定向植入1.5 mm深度的FMD。激光强度为1,064 nm，功率分别为0(对照组)、100 mW和200 mW，同时CED注入脂质体罗丹明(LR)或Gd-Evans蓝-血清白蛋白偶联络合物(Gd-EBA)，流速为0.1mU·L/min，持续1h。在输液过程中监测管路压力。结果经方差分析表明，联合给药显著增加了体积弥散，100 mW组体积为15.80.6 mm(3)，对照组为10.0+/-0.4 mm(3)，200 mW组为18.0+/-0.3 mm(3)，而仅液体对照组为10.3+/-0.7 mm(3)。200 mW联合照射组的脑组织出现热损伤，而100 mW联合照射组大鼠脑组织细胞结构得到保护。结论致死性和亚致死性光热疗法均能显著提高CED输注1h的体积弥散率。这表明，FMD联合给药方法可以减少CED过程中的输液次数和向大脑插入导管的次数。激光外科医生。2013年45：418-426。(C)2013年威利期刊公司。
Background and ObjectivesA fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064nm laser energy in an in vivo rodent model.Materials and MethodsFMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5mm. Laser irradiation (1,064nm) at 0 (control), 100, and 200mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 mu l/min for 1hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses.ResultsAnalysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.80.6mm(3) for 100mW compared to 10.0 +/- 0.4mm(3) for its fluid only control and 18.0 +/- 0.3mm(3) for 200mW compared to 10.3 +/- 0.7mm(3) for its fluid only control. Brains treated with 200mW co-delivery exhibited thermal lesions, while 100mW co-deliveries were associated with preservation of brain cytoarchitecture.ConclusionBoth lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures. Lasers Surg. Med. 45:418-426, 2013. (c) 2013 Wiley Periodicals, Inc.