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BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.
J Control Release 2017; 255:36-44JC

Abstract

Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin.

Authors+Show Affiliations

Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA; Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Life Sciences School of Hubei University, 368 Youyi Road, Wuhan 430062, China.Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA; College of Pharmaceutical Sciences, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310032, China.Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA.Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA. Electronic address: mwu5@mgh.harvard.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28390901

Citation

Chen, Fan, et al. "BCG Vaccine Powder-laden and Dissolvable Microneedle Arrays for Lesion-free Vaccination." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 255, 2017, pp. 36-44.
Chen F, Yan Q, Yu Y, et al. BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination. J Control Release. 2017;255:36-44.
Chen, F., Yan, Q., Yu, Y., & Wu, M. X. (2017). BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination. Journal of Controlled Release : Official Journal of the Controlled Release Society, 255, pp. 36-44. doi:10.1016/j.jconrel.2017.03.397.
Chen F, et al. BCG Vaccine Powder-laden and Dissolvable Microneedle Arrays for Lesion-free Vaccination. J Control Release. 2017 06 10;255:36-44. PubMed PMID: 28390901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination. AU - Chen,Fan, AU - Yan,Qinying, AU - Yu,Yang, AU - Wu,Mei X, Y1 - 2017/04/05/ PY - 2016/12/15/received PY - 2017/03/17/revised PY - 2017/03/31/accepted PY - 2017/4/10/pubmed PY - 2018/3/9/medline PY - 2017/4/10/entrez KW - BCG powder KW - Lesion-free KW - Microneedles KW - Skin delivery SP - 36 EP - 44 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 255 N2 - Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/28390901/BCG_vaccine_powder_laden_and_dissolvable_microneedle_arrays_for_lesion_free_vaccination_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(17)30510-2 DB - PRIME DP - Unbound Medicine ER -