Journal
BIOMATERIALS
Volume 81, Issue -, Pages 93-103Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.12.007
Keywords
Hyaluronate; Peptide; Conjugate; Transdermal; Vaccine
Funding
- Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea [HI14C1658]
- Bio & Medical Technology Development Program through the National Research Foundation (NRF) of Korea - MEST [2012M3A9C6049791]
- National Research Foundation of Korea [2012M3A9C6049791] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Duchenne's muscular dystrophy (DMD) is a neuromuscular disorder accompanied with muscle weakness and wasting. Since myostatin was reported to be a key regulator of muscle wasting, myostatin inhibitors have been investigated as therapeutic candidates for the treatment of muscular diseases. Here, we report an antigenic peptide of myostatin fragment (MstnF) conjugated to hyaluronate (HA) with a low molecular weight (MW, 17 kDa) for transdermal immunotherapy of DMD. Facilitating the transdermal delivery, the low MW HA showed a boosting effect on the immunization of MstnF possibly by engaging both toll-like receptors and cluster of differentiation 44 (CD44). In vivo two-photon microscopy clearly visualized the effective transdermal penetration of HA-MstnF conjugates into deep intact skin layers. The transdermal immunization of mdx mice significantly increased antibody titers against myostatin. Furthermore, the mdx mice immunized with HA-MstnF conjugates resulted in statistically significant improvement in the biochemical and pathological status of skeletal musculature as well as functional behaviors. (C) 2015 Elsevier Ltd. All rights reserved.
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