TY - JOUR
T1 - Biocompatible ionic liquids assisted transdermal co-delivery of antigenic protein and adjuvant for cancer immunotherapy
AU - Chowdhury, Md Raihan
AU - Moshikur, Rahman Md
AU - Wakabayashi, Rie
AU - Moniruzzaman, Muhammad
AU - Goto, Masahiro
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Science (JSPS) (KAKENHI No. JP16H06369, and JP20K20440). Victoria Muir, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) edited a draft of this manuscript.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5/15
Y1 - 2021/5/15
N2 - Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin—the stratum corneum—acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVA-specific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.
AB - Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin—the stratum corneum—acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVA-specific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.
UR - http://www.scopus.com/inward/record.url?scp=85104751551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104751551&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2021.120582
DO - 10.1016/j.ijpharm.2021.120582
M3 - Article
C2 - 33872711
AN - SCOPUS:85104751551
SN - 0378-5173
VL - 601
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 120582
ER -
