Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

Ehsan Afzal,¹ Saba Zakeri,¹ Peyman Keyhanvar,² Meisam Bagheri,^3,4 Parvin Mahjoubi,⁵ Mahtab Asadian,⁵ Nogol Omoomi,⁵ Mohammad Dehqanian,⁶ Negar Ghalandarlaki,¹ Tahmineh Darvishmohammadi,¹ Fatemeh Farjadian,⁷ Mohammad Sadegh Golvajoee,¹ Shadi Afzal,⁸ Maryam Ghaffari,⁹ Reza Ahangari Cohan,¹⁰ Amin Gravand,¹¹ Mehdi Shafiee Ardestani<sup>12,13

1</sup>Department of Biology, Science and Research Branch, Islamic Azad University, ²School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; ³Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India; ⁴Autoimmune Disease Research Center, Shiraz University of Medical Sciences, Shiraz, ⁵National Cell Bank, Pasteur Institute of Iran, ⁶Department of Nanotechnology, Faculty of Advanced Sciences and Technologies, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, ⁷Department of Chemistry, College of Science, Shiraz University, Shiraz, ⁸Department of English, Beyza Branch, Islamic Azad University, Beyza, ⁹Department of Basic Science at Apadana Education Institute, Shiraz, ¹⁰Department of Virology, Pasteur Institute of Iran, Tehran, ¹¹Faculty of Pharmacy, Ahwaz Jondishapour University of Medical Sciences, Ahwaz, ¹²Department of Medicinal Chemistry and Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, ¹³Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion – like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug.
Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated.
Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

Keywords: muscular dystrophy, glatiramer acetate, MyoD factor, drug delivery