一次性局部给药后，杂化树状聚合物水凝胶/ PLGA纳米颗粒平台维持药物递送持续1周，抗青光眼作用持续4天。,ACS Nano

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一次性局部给药后，杂化树状聚合物水凝胶/ PLGA纳米颗粒平台维持药物递送持续1周，抗青光眼作用持续4天。
ACS Nano ( IF 15.8 ) Pub Date : 2012-08-21 00:00:00 , DOI: 10.1021/nn301873v
Hu Yang _{1,

2} , Puneet Tyagi ₃ , Rajendra S. Kadam ₃ , Christopher A. Holden ₁ , Uday B. Kompella ₃

Affiliation

我们报道了两种抗青光眼药物，溴莫尼定和马来酸噻吗洛尔的新型递质的新型杂化聚酰胺酰胺（PAMAM）树状聚合物水凝胶/聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒平台（HDNP）。该平台对人角膜上皮细胞无细胞毒性。树枝状聚合物水凝胶显着增加了包囊尼罗红的PLGA纳米颗粒的细胞摄取。通过研究装入树枝状聚合物水凝胶中的FluoSpheres，可以证明纳米颗粒的停留时间延长。溴莫尼定和马来酸替莫洛尔均在体外缓慢释放在28-35天的时间内。在血压正常的成年荷兰带状雄兔中局部滴眼液（30μL0.7％w / v溴莫尼定和3.5％w / v马来酸替莫洛尔）局部滴眼后，HDNP制剂导致持续有效的IOP降低（18％或更高）的4天。此外，与盐水，DH和PLGA纳米颗粒剂型相比，HDNP在房水和角膜中的溴莫尼定浓度以及在房水，角膜和结膜中的马来酸替莫洛尔的浓度都显着提高了7天（与盐水，DH和PLGA纳米剂相比），而不会引起眼部炎症还是不舒服角膜和结膜的组织学分析未发现任何形态或结构变化。我们的工作表明，该新平台能够在更长的时间内增强药物的生物利用度并保持有效的IOP降低。这个新开发的平台可以大大减少局部用药的给药频率，从而改善患者的长期依从性并降低巨大的社会和经济成本。鉴于其高度的结构适应性，许多其他慢性眼部疾病将从该新平台的长期药物输送中受益。

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Hybrid Dendrimer Hydrogel/PLGA Nanoparticle Platform Sustains Drug Delivery for One Week and Antiglaucoma Effects for Four Days Following One-Time Topical Administration

We report a novel hybrid polyamidoamine (PAMAM) dendrimer hydrogel/poly(lactic-co-glycolic acid) (PLGA) nanoparticle platform (HDNP) for codelivery of two antiglaucoma drugs, brimonidine and timolol maleate. This platform was not cytotoxic to human corneal epithelial cells. Cellular uptake of Nile red-encapsulating PLGA nanoparticles was significantly increased by dendrimer hydrogel. A prolonged residence time of nanoparticles was demonstrated through investigation of FluoSpheres loaded into dendrimer hydrogel. Both brimonidine and timolol maleate were slowly released in vitro over a period of 28–35 days. Following topical administration of one eye drop (30 μL of 0.7% w/v brimonidine and 3.5% w/v timolol maleate) in normotensive adult Dutch-belted male rabbits, the HDNP formulation resulted in a sustained and effective IOP reduction (18% or higher) for 4 days. Furthermore, the HDNP maintained significantly higher concentrations of brimonidine in aqueous humor and cornea as well as timolol maleate in the aqueous humor, cornea, and conjunctiva up to 7 days as compared to saline, DH, and PLGA nanoparticle dosage forms, without inducing ocular inflammation or discomfort. Histological analysis of the cornea and conjunctiva did not reveal any morphological or structural changes. Our work demonstrated that this new platform is capable of enhancing drug bioavailability and sustaining effective IOP reduction over an extended period of time. This newly developed platform can greatly reduce dosing frequency of topical formulations, thus, improving long-term patient compliance and reducing enormous societal and economic costs. Given its high structural adaptability, many other chronic ocular diseases would benefit from long-lasting drug delivery of this new platform.

更新日期：2012-08-21

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