Development of liposomal systems for the release of alpha-glucosidase as a proposal for Pompe disease therapy

Pompe’s disease is caused by the deficiency of the lysosomal enzyme α-glycosidase acid (GAA) resulting in the accumulation of glycogen in the cells. The main tissues affected are cardiac, smooth and skeletal muscle and nervous. The clinical spectrum comprises a child form, more severe with high morbidity and mortality, and a late form, with slower progression, which causes muscle weakness and respiratory failure. The currently available therapy consists of enzyme replacement with a recombinant enzyme and represented a significant improvement in the patients’ life expectancy. Despite this, some factors still limit its benefits, such as the low availability and absorption of the free enzyme by the target cells, not interrupting the progression of the disease. Thus, the use of nanotechnology in the development of drug delivery systems appears as an alternative to overcome the difficulties of applying the free enzyme in the bloodstream. Among the available systems, liposomes represent an advanced technology for carrying active molecules. Liposomes are biocompatible and biodegradable lipid vesicular structures that allow delivery of the agent into cells or cellular compartments. The coating of the liposomal surface with hydrophilic components, such as polyethylene glycol (PEG), significantly increases its circulation time. Furthermore, specific ligands, such as antibodies, have been incorporated into the surface of these liposomes, seeking active targeting to a target site. As a result, the use of a long-circulating liposomal carrier functionalized with the antibody to the insulin receptor may result in greater distribution of the GAA enzyme to the target tissues, decreasing the necessary therapeutic dose and overcoming the current barriers for an adequate treatment of the Pompe’s disease.