Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice

详细信息    查看全文

• 作者：I-Chi Lee ; Wei-Ming Lin ; Jwu-Ching Shu ; Shau-Wei Tsai ; Chih-Hao Chen and Meng-Tsan Tsai
• 刊名：Journal of Biomedical Materials Research Part A
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：105
• 期：1
• 页码：84-93
• 全文大小：704K
• ISSN：1552-4965

文摘

Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy.