A detachable dissolving microneedles patch as a new effective platform to deliver Japanese encephalitis live attenuated chimeric vaccine

被引:1
作者
Dumkliang, Ekachai [1 ,2 ]
Suriyaamporn, Phuvamin [1 ]
Patrojanasophon, Prasopchai [1 ]
Ngawhirunpat, Tanasait [1 ]
Rojanarata, Theerasak [1 ]
Opanasopit, Praneet [1 ]
Yoksan, Sutee [3 ]
Pamornpathomkul, Boonnada [1 ,4 ]
机构
[1] Silpakorn Univ, Fac Pharm, Dept Ind Pharm, Pharmaceut Dev Green Innovat Grp PDGIG, Nakhon Pathom 73000, Thailand
[2] Prince Songkla Univ, Fac Pharmaceut Sci, Drug Delivery Syst Excellence Ctr DDSEC, Dept Pharmaceut Technol, Hat Yai 90110, Thailand
[3] Mahidol Univ, Mahidol, Thailand
[4] Silpakorn Univ, Fac Pharm, Dept Ind Pharm, Nakhon Pathom 73000, Thailand
关键词
Japanese encephalitis vaccine; Live attenuated chimeric vaccine; Detachable dissolving microneedles; Intradermal immunization; TRANSDERMAL DELIVERY; PROTECTIVE EFFICACY; DRUG-DELIVERY; IMMUNOGENICITY; NANOPARTICLES; IMMUNIZATION; MUCOSAL; RECOMMENDATIONS;
D O I
10.1016/j.jddst.2024.105377
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of this study was to develop a detachable dissolving microneedles (dDMNs) patch incorporating Japanese encephalitis live attenuated chimeric vaccine (JE-CV) via skin intradermal (ID) immunization. JE-CV-loaded dDMNs (JE-CV:dDMNs at a mass ratio of 1:4) were successfully formulated from NaHCO3:CS:PVA (sodium bicarbonate:chitosan:polyvinyl alcohol) at 0.25:1:4 mass ratio with 121 needles per patch of 1 cm(2). The MN patches showed sufficient mechanical strength to resist compression and maintain their appearance after penetrating excised neonatal porcine skin. After application, the MNs arrays were completely detachable from the backing layer at 1 h (similar to 91 % of delivery efficiency) as wearing time required, and over 80 % of the needles had dissolved after 2 h. For immune responses, the results found that mice immunized with a half-dose of the JE-CV via ID using a JE-CV-loaded dDMNs patch elicited seroprotection (PRNT50 >= 10 titers, recommended by the World Health Organization (WHO)) comparable to mice who received a full dose of the JE-CV via subcutaneous (SC) injection. In contrast, mice immunized with a half-dose of the JE-CV via SC injection did not elicit seroprotection. Mice immunized with a half-dose of the JE-CV-loaded dDMNs via ID stimulated IgA higher than mice immunized with the full-dose similar to 1.4 times in saliva and nasal wash. For cytokines' levels, mice immunized with the full-dose of the JE-CV solution via SC induced interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), the levels were similar to the half-dose of the JE-CV-loaded dDMNs patch ID immunization (p > 0.05). The results revealed that the JE-CV-loaded dDMNs showed promise for effectively stimulating humoral immune responses (HIR) and cell-mediated immune responses (CMIR) to protect against JEV.
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页数:16
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