Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.
It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 μm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 μm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery.
Fight Against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-744, Republic of Korea.
Hyun Beom
HB
Song
Department of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
Kang Ju
KJ
Lee
Department of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
Il Ho
IH
Seo
Department of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
Ji Yong
JY
Lee
Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang 431-070, Republic of Korea.
Sang-Mok
SM
Lee
Fight Against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
Jin Hyoung
JH
Kim
Fight Against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-744, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul 110-744, Republic of Korea. Electronic address: steph25@snu.ac.kr.
Jeong Hun
JH
Kim
Department of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: whryu@yonsei.ac.kr.
WonHyoung
W
Ryu
D060433:Administration, Ophthalmic; D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy*; D016503:Drug Delivery Systems; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009339:Needles; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib
Angiogenesis; Drug delivery; Impact insertion; Microneedle; Mouse cornea; Transfer molding