Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery

Abstract

Purpose: It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as cornea. The aim of this study is to demonstrate safety and efficacy of newly designed microneedle pen (MNP) system, a single microneedle (MN) with a spring-loaded applicator to provide impact insertion.

Methods: Desired shape of master mold was fabricated by KOH wet etching of silicon wafer. PDMS cavity molds were fabricated from the master mold and used for transfer-molding to attach MN to the tip of a spring-loaded applicator. A mixture of drug and carrier materials was prepared and loaded on the surface of MN tips using a dip coating method. Rhodamine B, Evans blue, or sunitinib malate were used as model drugs in this experiment. To investigate the localized delivery and the safety of MNPs, MNs coated with Evans blue were applied to mouse corneas and area of distribution and corneal thickness were compared with methods using 30G hypodermic needles. To investigate the efficacy of MNPs in delivering drugs, we delivered sunitinib malate with MNPs and evaluated their inhibitory effect on suture-induced corneal angiogenesis. Right after the intrastromal suture, sunitinib malate was delivered and corneal neovascularization was evaluated on the eighth day after injection.

Results: MN made of SU-8 had the base area of 200 × 200 µm² and the height of 140 µm. Application of MNPs on mouse cornea successfully delivered rhodamine dye to the stroma without perforation. When compared with delivery of Evans blue using 30G needle syringe or 30G needle tip, MNPs achieved the smallest area of distribution (886 ± 64 μm²) and left no evidence of corneal edema on the next day. Delivery of sunitinib malate with MNPs to suture-induced corneal angiogenesis model effectively decreased vessel length and clock hour of vascularization while delivery with 30G needle tip had no effect.

Conclusions: We designed a novel applicator that enables a targeted and impact-insertion of a MN in order to deliver drugs to thin tissues with little background support such as corneas. To enhance applicability of MN to macro-applicator, we applied transfer molding process. The fabricated MNPs could achieved a localized, minimally invasive and effective drug delivery to tissues without much background support.