title: BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.
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.affiliation: 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.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009339:Needles; D011208:Powders; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000295:instrumentation* / Q000379:methods
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D007074:Immunoglobulin G; D011208:Powders
keywords: BCG powder; Lesion-free; Microneedles; Skin delivery