Premium
Formulation of two‐layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice
Author(s) -
Lee IChi,
Lin WeiMing,
Shu JwuChing,
Tsai ShauWei,
Chen ChihHao,
Tsai MengTsan
Publication year - 2017
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35869
Subject(s) - transdermal , insulin , materials science , gelatin , biomedical engineering , bioavailability , in vivo , drug delivery , ex vivo , carboxymethyl cellulose , pharmacology , chromatography , chemistry , sodium , medicine , nanotechnology , in vitro , biochemistry , microbiology and biotechnology , metallurgy , biology
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. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84–93, 2017.