Polyplex-releasing microneedles for enhanced cutaneous delivery of DNA vaccine.
Microneedle (MN)-based DNA vaccines have many advantages over conventional vaccines administered by hypodermic needles. However, an efficient strategy for delivering DNA vaccines to intradermal cells has not yet been established. Here, we report a new approach for delivering polyplex-based DNA vaccines using MN arrays coated with a pH-responsive polyelectrolyte multilayer assembly (PMA). This approach enabled rapid release of polyplex upon application to the skin. In addition to the polyplex-releasing MNs, we attempted to further maximize the vaccination by developing a polymeric carrier that targeted resident antigen presenting cells (APCs) rich in the intradermal area, as well as a DNA vaccine encoding a secretable fusion protein containing amyloid beta monomer (Aβ1-42), an antigenic determinant. The resulting vaccination system was able to successfully induce a robust humoral immune response compared to conventional subcutaneous injection with hypodermal needles. In addition, antigen challenge after immunization elicited an immediate and strong recall immune response due to immunogenic memory. These results suggest the potential utility of MN-based polyplex delivery systems for enhanced DNA vaccination.
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Nak Won
NW
Kim
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Min Sang
MS
Lee
The Graduate School of Nanoscience & Technology (WCU), Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea.
Kyu Ri
KR
Kim
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jung Eun
JE
Lee
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Kyuri
K
Lee
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jong Sung
JS
Park
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan.
Yoh
Y
Matsumoto
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Dong-Gyu
DG
Jo
The Graduate School of Nanoscience & Technology (WCU), Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea.
Haeshin
H
Lee
School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Doo Sung
DS
Lee
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jhjeong@skku.edu.
Ji Hoon
JH
Jeong
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D004867:Equipment Design; D005260:Female; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D006863:Hydrogen-Ion Concentration; D056724:Immunity, Humoral; D007114:Immunization; D007156:Immunologic Memory; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008904:Miniaturization; D009339:Needles; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D011108:Polymers / Q000737:chemistry*; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D011108:Polymers; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)
DNA vaccine; Gene delivery; Layer-by-layer assembly; Microneedle array; pH-responsive materials