Chen Jianmin, Qiu Yuqin, Zhang Suohui, Gao Yunhua
a College of Pharmaceutical and Medical Technology, Putian University , Fujian , China and.
b Key Laboratory of Photochemical Conversion and Optoelectronic Materials , Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , Beijing , China.
Drug Dev Ind Pharm. 2016;42(6):890-6. doi: 10.3109/03639045.2015.1096282. Epub 2015 Oct 15.
The dermal and transdermal delivery of protein pharmaceuticals faces enormous challenges, and at the same time, has very significant potential for the non-invasive treatment of both localized and systemic diseases. To demonstrate the pharmaceutical usefulness of dissolving microneedles (MNs) containing interferon-α-2b (IFN), IFN MNs were prepared using a new method. IFN were encapsulated in MNs with dose from 4.94 ± 0.64 to 23.79 ± 2.48 μg, and in vitro release test showed the efficiency reached 49.2%. After percutaneous administration of IFN MNs to rats, serum IFN levels were measured for 12 h. The peak serum IFN level, maximum drug concentration (Cmax), and the time to reach maximum concentration (Tmax), were 11.58 ± ng/ml and 40 min, respectively, for high-dose MNs group. The area under the curve (AUC) of MNs group was 28.85 ng·h/ml, while intramuscular injection (IM) group with equal dose was 31.17 ng·h/ml. Immunogenicity analysis showed the anti-IFN antibody got back to normal level at ninth week, and there was no difference between male and female rats. IFN MNs showed good stability for 2 months and no damage to the administered rats' skin. The results demonstrated the IFN MNs have a great potential to provide an alternative to IM.
蛋白质药物的真皮和透皮给药面临巨大挑战，但同时，对于局部和全身性疾病的非侵入性治疗具有非常显著的潜力。为了证明含有干扰素-α-2b（IFN）的溶解微针（MNs）的药物实用性，采用一种新方法制备了IFN微针。IFN被封装在微针中，剂量为4.94±0.64至23.79±2.48μg，体外释放试验表明释放效率达到49.2%。将IFN微针经皮给予大鼠后，测量12小时的血清IFN水平。高剂量微针组的血清IFN峰值水平、最大药物浓度（Cmax）和达到最大浓度的时间（Tmax）分别为11.58±ng/ml和40分钟。微针组的曲线下面积（AUC）为28.85ng·h/ml，而等剂量肌肉注射（IM）组为31.17ng·h/ml。免疫原性分析表明，抗IFN抗体在第九周恢复到正常水平，雄性和雌性大鼠之间没有差异。IFN微针在两个月内表现出良好的稳定性，对给药大鼠的皮肤没有损伤。结果表明，IFN微针有很大潜力成为肌肉注射的替代方法。
