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Bleomycin-Coated Microneedles for Treatment of Warts

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Abstract

Purpose

Bleomycin-coated microneedles were devised for delivery of bleomycin into the sub-epidermal skin layer for the treatment of warts in order to provide patient convenience and reduce patient pain and fear.

Method

Poly-lactic-acid (L-PLA) microneedles were fabricated by a molding process and then the tips were partially coated using a dip-coating method based on a microstructure well. The mechanical strength of the pre-coated polymer microneedles was observed by inserting them in porcine foot and back skin. The holes were stained with trypan blue and the mechanical failure of the microneedles was investigated using a scanning electron microscope (SEM). The initial distribution of a model drug using microneedles was compared with distribution by intralesional injection. The amount of drug leaked below the skin using microneedles was measured and compared with that leaked by intralesional injection. The pharmacokinetic properties of bleomycin-coated microneedles were studied. The bleomycin remaining on the coated microneedles after the in vivo pharmacokinetic study was measured.

Results

Bleomycin was successfully coated on the tips of L-PLA microneedles. More than 80% of the bleomycin dissolved into the skin in vitro within 15 min. L-PLA microneedles possessed sufficient mechanical strength to penetrate skin with a thick stratum corneum. Compared to intralesional injection, tip-coated microneedles were more effective in distributing a drug into the sub-epidermal skin layer. A pharmacokinetic study of bleomycin-coated microneedles showed 50 min of Tmax.

Conclusions

Bleomycin-coated microneedles appeared to be a convenient and painless alternative to conventional intralesional injection of bleomycin. The microneedles delivered bleomycin into the targeted dermal layer regardless of body site. Bleomycin-coated microneedles therefore provide a suitable method for the treatment of warts.

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Abbreviations

CMC:

Carboxy-methyl-cellulose

HPV:

Human papillomavirus

LC/MS/MS:

Liquid chromatography-mass spectrometry

L-PLA:

Poly L-lactic acid

PK:

Pharmacokinetic

PLGA:

Poly dl-lacide-co-glycolide

SC:

Subcutaneous

SEM:

Scanning electron microscope

UV:

Ultraviolet

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported by the Gachon University Gil Medical Center (Grant number: 2013-47) a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea.

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Authors and Affiliations

  1. Department of BioNano Technology and Gacheon BioNano Research Institute, Gachon University, Seongnam, Korea

    Han Sol Lee & Jung-Hwan Park

  2. Department of Dermatology, Gachon University Gil Medical Center, Incheon, Korea

    Ha Ryeong Ryu & Joo Young Roh

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  1. Han Sol Lee
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  2. Ha Ryeong Ryu
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  4. Jung-Hwan Park
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Correspondence to Joo Young Roh or Jung-Hwan Park.

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Lee, H.S., Ryu, H.R., Roh, J.Y. et al. Bleomycin-Coated Microneedles for Treatment of Warts. Pharm Res 34, 101–112 (2017). https://doi.org/10.1007/s11095-016-2042-x

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  • DOI: https://doi.org/10.1007/s11095-016-2042-x

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