Liposomal steroid nano-drug is superior to steroids as-is in mdx mouse model of Duchenne muscular dystrophy.

Abstract

Glucocorticosteroids are the most efficacious anti-inflammatory agents and the gold standard treatment in Duchenne muscular dystrophy (DMD). However, their chronic use may lead to severe side effects. We evaluated the use of a novel injectable steroidal nano-drug in mdx mouse model of DMD by comparing the efficacy of nano-liposomes remotely loaded with the steroid prodrug, methylprednisolone hemisuccinate (MPS) with the same steroid as-is, in short (4-weeks) and long-term (58-weeks) treatments. Liposomal-MPS was selectively targeted to the mouse diaphragm, the most dystrophic muscle at early stage of the disease. The bioactivity of the steroidal nano-drug was evidenced by a significant decreased serum TGF-β and reduced diaphragm macrophage infiltration after short-term treatment. In the long-term, the treatment with liposomal-MPS not only demonstrated improved muscle strength and mobility it also induced lower tibia and lumbar vertebrae osteoporosis indicating much lower bone related adverse effects.

• Authors: Keren Turjeman, Nurit Yanay, Moran Elbaz, Yaelle Bavli, Moria Gross, Malcolm Rabie, Yechezkel Barenholz, Yoram Nevo
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 16 Pg. 34-44 (02 2019) ISSN: 1549-9642 [Electronic] United States
• PMID: 30529791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Liposomes
• Steroids
• Transforming Growth Factor beta
• Creatine Kinase

Topics

• Animals
• Creatine Kinase (metabolism)
• Disease Models, Animal
• Immunohistochemistry
• Inflammation (blood, drug therapy)
• Liposomes (chemistry)
• Male
• Mice
• Mice, Inbred mdx
• Muscle Strength (drug effects)
• Muscular Dystrophy, Duchenne (blood, drug therapy)
• Steroids (chemistry, therapeutic use)
• Transforming Growth Factor beta (blood)