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. 2017 Feb 10;12(2):e0172043.
doi: 10.1371/journal.pone.0172043. eCollection 2017.

Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery

Jiyu Li  1 , Bin Liu  1 , Yingying Zhou  1 , Zhipeng Chen  1 , Lelun Jiang  1 , Wei Yuan  2 , Liang Liang  2
Affiliations

Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery

Jiyu Li et al. PLoS One. .

Abstract

Microneedle arrays (MA) have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA) fabricated by modified metal injection molding (MIM) technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Fabrication process sketch for TPMA.
Fig 2
Fig 2. Solid-state sintering process curve for TPMA.
Fig 3
Fig 3. Setup for penetration performance test of TPMA.
Fig 4
Fig 4
In vitro permeation studies using vertical Franz diffusion cells via (a) punctured rabbit skin, (b) TPMA with punctured rabbit skin, and (c) untreated rabbit skin.
Fig 5
Fig 5
The morphology of: (a-d) TMA green body and (e-h) TPMA.
Fig 6
Fig 6. The element content of TPMA analyzed by EDS.
(a-b) Elements at the surface of micro-needle and (c-d) elements on the base.
Fig 7
Fig 7. The relationship between the resistance force and impendence during the TPMA compression process.
Fig 8
Fig 8
(a) The rabbit skin punctured by TPMA with Rhodamine B and (b) the drug diffusion fluorescence image of punctured skin slices at different depth.
Fig 9
Fig 9. In vitro cumulative permeated amount of calcein across TPMA with punctured skin, punctured skin, and untreated skin.
The results are expressed as the mean ± standard deviation of three experiments.
See this image and copyright information in PMC

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