TY - JOUR
T1 - Polymeric microneedle-mediated transdermal delivery of melittin for rheumatoid arthritis treatment
AU - Du, Guangsheng
AU - He, Penghui
AU - Zhao, Jiaxuan
AU - He, Chunting
AU - Zhang, Zhihua
AU - Zhang, Zhibing
AU - Sun, Xun
PY - 2021/8/10
Y1 - 2021/8/10
N2 - Transdermal drug delivery systems for rheumatoid arthritis (RA) have been receiving increasing attention as they can potentially overcome drawbacks which exist in traditional oral or injection strategies, including low patient compliance and serious gastrointestinal side effects. However, transdermal delivery of RA drugs especially biological drugs suffers from low drug delivery efficiency due to the robust skin barrier. Herein, we fabricated melittin-loaded hyaluronic acid (HA) microneedles and investigated their capacity for inhibiting RA. We showed that melittin-loaded HA microneedles possessed high mechanical strength for successful delivery of melittin into the skin and effectively inhibited RA progression in adjuvant induced both rodent and murine models, as shown by results in histological, paw swelling and arthritis score. Furthermore, after modifying HA with cross-linkable groups, the fabricated microneedles with sustained release properties could further improve the therapeutic potency. Cytokine and T cell analysis in the paws and lymphatic organs indicated that the application of microneedles suppressed the levels of pro-inflammation cytokines including IL-17 and TNF-α, and increased the percentage of regulatory CD4 T cells. Our study revealed that polymeric microneedle-mediated transdermal delivery of melittin could serve as a new therapy with high compliance and good therapeutic efficacy for RA and other autoimmune diseases.
AB - Transdermal drug delivery systems for rheumatoid arthritis (RA) have been receiving increasing attention as they can potentially overcome drawbacks which exist in traditional oral or injection strategies, including low patient compliance and serious gastrointestinal side effects. However, transdermal delivery of RA drugs especially biological drugs suffers from low drug delivery efficiency due to the robust skin barrier. Herein, we fabricated melittin-loaded hyaluronic acid (HA) microneedles and investigated their capacity for inhibiting RA. We showed that melittin-loaded HA microneedles possessed high mechanical strength for successful delivery of melittin into the skin and effectively inhibited RA progression in adjuvant induced both rodent and murine models, as shown by results in histological, paw swelling and arthritis score. Furthermore, after modifying HA with cross-linkable groups, the fabricated microneedles with sustained release properties could further improve the therapeutic potency. Cytokine and T cell analysis in the paws and lymphatic organs indicated that the application of microneedles suppressed the levels of pro-inflammation cytokines including IL-17 and TNF-α, and increased the percentage of regulatory CD4 T cells. Our study revealed that polymeric microneedle-mediated transdermal delivery of melittin could serve as a new therapy with high compliance and good therapeutic efficacy for RA and other autoimmune diseases.
KW - Hyaluronic acid
KW - Melittin
KW - Polymeric microneedles
KW - Rheumatoid arthritis
KW - Sustained release
UR - http://www.scopus.com/inward/record.url?scp=85109464895&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2021.07.005
DO - 10.1016/j.jconrel.2021.07.005
M3 - Article
SN - 0168-3659
VL - 336
SP - 537
EP - 548
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -