Azam Safary
1,2 
, Mostafa Akbarzadeh Khiavi
3,2 , Rahimeh Mousavi
2, Jaleh Barar
2,4 , Mohammad A Rafi
5*1 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
3 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5 Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvanian 19107, USA
Abstract
Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these shortcomings necessitate the development of more effective diagnosis and treatment modalities against LSDs. Taken all, maximizing the therapeutic response with minimal undesired side effects might be attainable by the development of targeted enzyme delivery systems (EDSs) as a promising alternative to the LSDs treatments, including different types of mucopolysaccharidoses (MPSs) as well as Fabry, Krabbe, Gaucher and Pompe diseases.