Dissolving Microneedle Patches for Transdermal Insulin Delivery in Diabetic Mice: Potential for Clinical Applications

被引:60
作者
Chen, Chih-Hao [1 ,2 ]
Shyu, Victor Bong-Hang [2 ]
Chen, Chien-Tzung [2 ,3 ]
机构
[1] Chang Gung Univ, Dept Chem & Mat Engn, Taoyuan 333, Taiwan
[2] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Dept Plast & Reconstruct Surg, Craniofacial Res Ctr,Coll Med, Taoyuan 333, Taiwan
[3] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp Keelung, Dept Plast & Reconstruct Surg, Keelung 204, Taiwan
关键词
microneedle; polymer; transdermal; insulin; diabetes mellitus; DRUG-DELIVERY; SKIN THICKNESS; POLYMER MICRONEEDLES; HUMAN VOLUNTEERS; PENETRATION; FORMULATION; FABRICATION; CHALLENGES; TRANSPORT; ARRAYS;
D O I
10.3390/ma11091625
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
In this study, dissolving polymeric microneedle (MN) patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were used to localize insulin. Their in vitro skin insertion capabilities were determined using tissue-marking dye to stain the skin after patches removal. Scanning electron microscopy (SEM) was used to determine changes in the MNs over time, and optical coherence tomography (OCT) was used to monitor their real-time penetration depth. Confocal microscopy images revealed that rhodamine 6G gradually diffuses from the puncture sites to deeper dermal tissue. Using an in vivo imaging system (IVIS), skin areas that received FITC-insulin-loaded MNs were found to present strong fluorescent signals that greatly decreased 1 h after application. Results show that dissolving MNs rapidly release FITC-insulin, and it then gradually diffuses into the skin. This study verifies that using a gelatin/CMC MN patch for insulin delivery achieves satisfactory relative bioavailability compared to a traditional hypodermic injection and can be a promising delivery device for poorly permeable protein drugs such as those used to treat diabetes. Insertion tests on human cadaveric skin demonstrate that dissolving MNs could serve as efficient devices for transdermal drug delivery in clinical practice and that the volar aspect of forearm skin is the ideal location for their applications.
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页数:10
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