A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin.
Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm-2) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics.
Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea.
Keum-Yong
KY
Seong
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, 88 Dongnae-ro, Dong-gu, Daegu 41061, Republic of Korea.
Min-Soo
MS
Seo
Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea.
Dae Youn
DY
Hwang
School of Mechanical and Materials Engineering, UCD Centre for Biomedical Engineering, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Eoin D
ED
O'Cearbhaill
3U Diabetes, Dept of Endocrinology, Royal College of Surgeons in Ireland, Connolly Hospital, Blanchardstown, Dublin 15, Ireland.
Seamus
S
Sreenan
Division of BioEngineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
Jeffrey M
JM
Karp
Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea. Electronic address: syang@pusan.ac.kr.
Seung Yun
SY
Yang
D000179:Acrylates / Q000737:chemistry*; D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009339:Needles; D010539:Permeability; D011137:Polystyrenes / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014018:Tissue Distribution; D057968:Transdermal Patch
D000179:Acrylates; D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D011137:Polystyrenes; C509855:poly(styrene-b-acrylic acid)
Insulin delivery; Mechanical interlocking; Microneedle; Transdermal patch