Abstract
Enzyme replacement therapies (ERT) have been of great help over the past 30 years in the treatment of various lysosomal storage disorders, including chronic pancreatitis and its common complication, exocrine pancreatic insufficiency. Research shows that difficulties in designing such drugs can be overcome by using appropriate additives and various enzyme immobilization techniques. Cyclodextrins (CDs) can be considered as a promising additive for enzyme replacement therapies, as they are known to enhance the activity of enzymes in a complex process due to their specific binding. In this study, we investigated the formulation of lipases (from Aspergillus oryzae and Burkholderia cepacia) paired with different cyclodextrins in poly(vinyl alcohol) (PVA) nanofibers by electrospinning technique. We examined the effect of the presence of cyclodextrins and nanoformulation on the lipase activity. The rheological and morphological characterizations of precursors and nanofibers were also performed using a viscometer as well as electron and Raman microscope. We found that by selecting the appropriate CD:lipase ratio, the activity of the investigated enzyme could be multiplied, and cyclodextrins can support the homogeneous dispersion of lipases inside the solid formula. In addition, the entrapment of lipases in PVA nanofibers led to a significant increase in activity compared to the preformulated precursor. In this way, the nanofibrous formulation of lipases combining CDs as additives can provide an efficient and sustainable possibility for designing novel solid medicines in ERT.
Highlights
In this study we investigate the effect of selected cyclodextrins on the enzymatic acIn this study we investigate the effect of selected cyclodextrins on the enzymatic tivity of lipases from two different strains (Burkholderia cepacia and Aspergillus oryzae), activity of lipases from two different strains (Burkholderia cepacia and Aspergillus oryzae), which are accepted enzymes in Pancreatic Enzyme Replacement Therapy (PERT)
We found that the activity of the tested lipases was very sensitive to the quality and quantity of cyclodextrins (CDs) used as an additive in the lipase-catalyzed hydrolysis of p-nitrophenyl palmitate
Of the five investigated CDs compared (β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin, randomly methylated β-cyclodextrin, sulfobutylated-βcyclodextrin), the two that caused the most remarkable increase in activity for both selected lipases were studied in more detail, and an optimal lipase:CD weight ratio was determined for both proteins, using the ratio with which the CDs significantly improved the catalytic activity of lipases
Summary
LSDs, such as Fabry disease, lysosomal acid lipase deficiency, Hurler syndrome, Hunter syndrome, and Maroteaux–Lamy syndrome [6,7]. While these methods are really effective at treating the symptoms of LSDs, they do not provide a solution for the inherent problem of insufficient enzyme production [8]. The biggest disadvantage of using ERTs, is that their effectiveness depends deeply on whether the ERT can be targeted to the disease-affected tissues. This often requires modifications to the enzyme, as purified enzymes are often not targeted to the lysosomes. Treating neurological symptoms poses a great challenge because ERTs that are given intravenously are unable to cross the blood–brain barrier
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