The targeting of drugs to skeletal muscle is an emerging area of research. Driven by the need for new therapies
to treat a range of muscle-associated diseases, these strategies aim to provide improved drug exposure at the site of action
in skeletal muscle with reduced concentration in other tissues where unwanted side effects could occur. By interacting
with muscle-specific cell surface recognition elements, both tissue localization and selective uptake into skeletal muscle
cells can be achieved. The design of molecules that are substrates for muscle uptake transporters can provide concentration
in m uscle tissue. For example, drug conjugates with carnitine can provide improved muscle uptake via OCTN2 transport. Binding to
muscle surface recognition elements followed by endocytosis can allow even large molecules such as antibodies to enter muscle cells.
Monoclonal antibody 3E10 demonstrated selective uptake into skeletal muscle in vivo. Hybrid adeno-associated viral vectors have recently
shown promise for high skeletal muscle selectivity in gene transfer applications. Delivery technology methods, including electroporation
of DNA plasmids, have also been investigated for selective muscle uptake. This review discusses challenges and opportunities
for skeletal muscle targeting, highlighting specific examples and areas in need of additional research.
Keywords: Tissue targeting, skeletal muscle, drug delivery, transporter, virus, antibody.
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