Erythropoietin-Coated ZP-Microneedle Transdermal System: Preclinical Formulation, Stability, and Delivery
Erythropoietin-Coated ZP-Microneedle Transdermal System: Preclinical Formulation, Stability, and Delivery
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DOI：
10.1007/s11095-012-0674-z
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发表时间：
2012-06-01
影响因子：
3.7
通讯作者：
Daddona, Peter E.
中科院分区：
文献类型：
--
作者：
Peters, Elaine E.;Ameri, Mahmoud;Daddona, Peter E.
为了评估将配制的重组人红细胞生成素α（EPO）涂覆在钛微针透皮给药系统ZP-EPO上的可行性，并评估临床前贴剂的给药性能，通过粘度测定和接触角测量来评估制剂流变学和表面活性。通过浸涂和干燥将EPO液体制剂涂覆到钛微针上。采用SEC-HPLC、CZE和效价测定等方法对包被EPO的稳定性进行了评价。在大鼠中进行了EPO涂层微针贴片的临床前递送和药代动力学研究，并与皮下EPO注射进行了比较。ZP-EPO贴剂在25 ℃下稳定至少3个月，聚集体%、同种型或效力没有显著变化。在大鼠中进行的临床前研究显示，涂有750 IU至22，000 IU的ZP-EPO微针贴片以高效率（75-90%）递送，具有线性剂量反应。结果表明微针透皮贴剂给药EPO是可行的，并可能提供一个有效的，剂量可调，患者友好的替代目前的静脉或皮下给药途径。
To evaluate the feasibility of coating formulated recombinant human erythropoietin alfa (EPO) on a titanium microneedle transdermal delivery system, ZP-EPO, and assess preclinical patch delivery performance.Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. EPO liquid formulation was coated onto titanium microneedles by dip-coating and drying. Stability of coated EPO was assessed by SEC-HPLC, CZE and potency assay. Preclinical delivery and pharmacokinetic studies were conducted in rats with EPO-coated microneedle patches and compared to subcutaneous EPO injection.Studies demonstrated successful EPO formulation development and coating on microneedle arrays. ZP-EPO patch was stable at 25A degrees C for at least 3 months with no significant change in % aggregates, isoforms, or potency. Preclinical studies in rats showed the ZP-EPO microneedle patches, coated with 750 IU to 22,000 IU, delivered with high efficiency (75-90%) with a linear dose response. PK profile was similar to subcutaneous injection of commercial EPO.Results suggest transdermal microneedle patch delivery of EPO is feasible and may offer an efficient, dose-adjustable, patient-friendly alternative to current intravenous or subcutaneous routes of administration.