Abstract
Thyroid hormones (active form T3) are naturally potent compounds that influence energy expenditure, cholesterol metabolism, and fat oxidation. T3 would be an effective anti-obesity drug if it would not be delivered to the heart and bones, which leads to serious side effects, such as cardiovascular and bone thyrotoxicity, muscle wasting, and so on. In this study, we designed a targeted drug delivery system that is a glucagon-modified liposome to deliver T3 to the liver and adipose tissues. The liposomes exhibited excellent properties, including uniform nanoscale particle size, good physicochemical stability, and adequate drug release behavior. More importantly, the glucagon-modified liposomes were enriched in the liver, which minimized the undesired bone and cardiovascular thyrotoxicity of T3. Compared to the control group, T3-loading glucagon-modified liposomes could effectively decrease body weight, reverse hepatic steatosis, and correct hyperlipidemia and hyperglycemia in ob/ob mice, without the undesired cardiovascular and bone thyrotoxicity. These findings indicate that delivery of thyroid hormone by glucagon-modified liposomes may provide an effective strategy for anti-obesity therapy.
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