李敏姝, 于翔, 金义光, 吴志鸿. 眼用微创布林佐胺可溶性微针J. 药学学报, 2021,56(3): 849-854. doi: 10.16438/j.0513-4870.2020-1436
引用本文: 李敏姝, 于翔, 金义光, 吴志鸿. 眼用微创布林佐胺可溶性微针J. 药学学报, 2021,56(3): 849-854. doi: 10.16438/j.0513-4870.2020-1436
LI Min-shu, YU Xiang, JIN Yi-guang, WU Zhi-hong. Minimally invasive dissolving microneedles for ocular brinzolamide deliveryJ. Acta Pharmaceutica Sinica, 2021,56(3): 849-854. doi: 10.16438/j.0513-4870.2020-1436
Citation: LI Min-shu, YU Xiang, JIN Yi-guang, WU Zhi-hong. Minimally invasive dissolving microneedles for ocular brinzolamide deliveryJ. Acta Pharmaceutica Sinica, 2021,56(3): 849-854. doi: 10.16438/j.0513-4870.2020-1436

眼用微创布林佐胺可溶性微针

Minimally invasive dissolving microneedles for ocular brinzolamide delivery

  • 摘要: 角膜屏障影响眼用药物的渗透及药效。本文选择难溶性药物布林佐胺作为模型药物,制备了其眼用角膜微创可溶性微针。将布林佐胺溶于乙醇,加入聚乙烯吡咯烷酮K90溶解后,灌注于微针模具中,干燥后脱模得到布林佐胺微针。体视镜和扫描电镜显示该微针为圆锥形,高约750 μm,底部直径约300 μm,针尖距约500 μm。微针贴片为10×10阵列,面积为1 cm2,载药量高达7.3 mg·cm2。布林佐胺微针的2 h体外释放率达93%,药物角膜渗透量为877±105 μg。微针机械强度较大(0.32 N/针),易插入大鼠角膜中,深度达200 μm,贴片在2 min内就可快速溶解,受损角膜于24 h内可快速修复。所有动物实验经军事医学研究院辐射医学研究所伦理委员会批准且实验均按照相关指导原则和规定进行。眼用微创可溶性微针具有角膜微创和快速修复、载药量大和渗透率高的特点,有很好的眼部疾病治疗应用前景。

     

    Abstract: The permeation and pharmacodynamics of ocular drugs are influenced by the corneal barrier. Here, a hard-soluble drug, brinzolamide, was selected as the model drug and used for preparation of minimally invasive dissolving microneedles. Brinzolamide was dissolved in ethanol and polyvinylpyrrolidone (PVP) K90 was added and dissolved. The mixture solution was casted into the dissolving microneedles mold and dried and brinzolamide dissolving microneedles (BMN) were obtained after demolding. The stereoscopic and scanning electron microscopic images showed that BMN were conical needles with the height of 750 μm, the bottom diameter of 300 μm, and the inter-tip distance of 500 μm. The dissolving microneedles patch was composed of 10×10 arrays with the area of 1 cm2 and the high drug load of 7.3 mg·cm-2. BMN showed a rapid in vitro drug release with 93% accumulative release at 2 h and the high drug corneal permeation amount of 877±105 μg. BMN exhibited the high mechanical strength of 0.32 N/needle, leading to easy rat corneal insertion with the depth of 200 μm. Moreover, BMN were rapidly dissolved in the cornea, and more importantly, the damaged cornea were quickly self-healed within 24 h. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical and the experiments were conducted in accordance with relevant guidelines and regulations. Ocular minimally invasive dissolving microneedles have the advantages of corneal minimal wounds and rapid healing, high drug loading, and high permeability, favoring the treatment of ocular diseases.

     

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