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Skin test of tuberculin purified protein derivatives with a dissolving microneedle-array patch

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Abstract

Background

The tuberculin skin test (TST) is a long-established screening method for tuberculosis. However, the Mantoux technique is often difficult to reliably perform, which affects testing results and safety, which causes local skin pain and pruritus.

Methods

In this study, dissolving microneedle-array patches (MNP) were used to deliver purified protein derivative (PPD) tuberculin into the skin. The skin reaction was compared between MNP delivery and conventional injection.

Results

The MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1 h. The storage life of MNP loaded with PPD (MNP-PPD) was 7 weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04 IU) was needed in MNP compared with conventional injection (2 IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.7 ± 5.6 mm in TB patients, 12.6 ± 4.4 mm in LTBI (latent TB infection) patients, and 5.8 ± 2.7 mm in BCG vaccination healthy volunteers and lasted approximately 26 ± 5.4 days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 ± 0.7 mm in TB patients and 2.0 ± 0.5 mm in LTBI, and the duration time was only 8.5 ± 1.5 days. Moreover, despite the relatively mild skin reactivity in BCG vaccination healthy volunteers with conventional injection, there was no skin reactivity in BCG vaccination healthy volunteers with MNP-PPD.

Conclusion

In addition to being minimally invasive, needle-free, and painless, no adverse effects were attributed to the new diagnostic method, which may be of value for the safe and effective clinical administration of TB screening. When applied with MNP-PPD, an area of redness and induration greater than 2.5 mm can identify a TB-positive patient.

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Abbreviations

TST:

Tuberculin skin test

TB:

Tuberculosis

MNP:

Microneedle-array patch

PPD:

Purified protein derivative tuberculin

LTBI:

Latent TB infection

BCG:

Bacillus Calmette-Guerin

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Research funding

This work was supported by National Key Research and Development Program of China (No. 2018YFC0809200), Guangdong Science and Technology Foundation (No. 2017A030313668, No. 2017B020210006), Shenzhen Science and Technology Foundation (No. CKCY20170720100145397, No. GJHS20170314161153714, No. JCYJ20170307104024209). The health and family planning commission of Wuhan municipality (WX17A09) and the Wuhan middle and young backbone talent program provided funding. The Natural Science Foundation of Hubei Province (ZRMS2019001095) also provided funding.

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Correspondence to Fan Chen.

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All of the studies were reviewed and approved by the Ethics Committee of Hubei University.

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Wei Wang, Hou Ming Liu, and Jing Zhou are joint first authors

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Wang, W., Liu, H.M., Zhou, J. et al. Skin test of tuberculin purified protein derivatives with a dissolving microneedle-array patch. Drug Deliv. and Transl. Res. 9, 795–801 (2019). https://doi.org/10.1007/s13346-019-00629-y

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