Controlled release of FK506 from micropatterned PLGA films: potential for application in peripheral nerve repair.
Controlled release of FK506 from micropatterned PLGA films: potential for application in peripheral nerve repair.
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DOI：
10.4103/1673-5374.235063
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发表时间：
2018-07
影响因子：
6.1
通讯作者：
Agarwal J
中科院分区：
文献类型：
--
作者：
Davis B;Wojtalewicz S;Labroo P;Shea J;Sant H;Gale B;Agarwal J
经过几十年的研究，周围神经损伤和修复仍然经常导致瘫痪、慢性疼痛和神经病变，导致患者严重残疾。目前临床上可用的神经导管只能提供粗糙的引导轴突通过神经间隙再生，没有额外的功能。FK506（他克莫司）是一种FDA批准的免疫抑制剂，已被证明可以增强周围神经再生，但在全身给药时具有严重的副作用。本研究的目的是开发和评估一种生物可吸收的药物递送系统，该系统能够局部扩展递送FK506，并提供拓扑引导线索，通过微沟槽引导轴突生长。采用光刻技术制备了嵌入FK506的聚乳酸-羟基乙酸（PLGA）微图型薄膜。制备了无图案化、10/10 μm（脊/槽宽度）和30/30 μm图案化膜，分别负载0、1和3 μg/cm2的FK506。体外FK506释放率测试表明，该薄膜能够延长（至少56天），控制和可扩展释放FK506。神经突延伸生物活性测定结果表明，FK506释放后（样品浓度为8.46 ~ 19.7 ng/mL）与对照FK506 （10 ng/mL FK506）的神经突延伸生物活性保持一致。本研究制备的多功能FK506包埋微图案聚乳酸-羟基乙酸膜在周围神经修复装置的构建中具有潜在的应用前景。
After decades of research, peripheral nerve injury and repair still frequently results in paralysis, chronic pain and neuropathies leading to severe disability in patients. Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality. FK506 (Tacrolimus), an FDA approved immunosuppressant, has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically. The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves. Photolithography was used to create micropatterned poly(lactide-co-glycolic acid) (PLGA) films embedded with FK506. Non-patterned, 10/10 μm (ridge/groove width), and 30/30 μm patterned films loaded with 0, 1, and 3 μg/cm2 FK506 were manufactured and characterized. In vitro FK506 rate of release testing indicated that the films are capable of an extended (at least 56 days), controlled, and scalable release of FK506. Neurite extension bioactivity assay indicated that FK506 released from the films (concentration of samples tested ranged between 8.46–19.7 ng/mL) maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages (10 ng/mL FK506). The multi-functional FK506 embedded, micropatterned poly(lactide-co-glycolic acid) films developed in this study have potential to be used in the construction of peripheral nerve repair devices.
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影响因子：
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通讯作者：
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