Nanofibrous Formulation of Cyclodextrin Stabilized Lipases for Efficient Pancreatin Replacement Therapies
Gergő Dániel Tóth,
Adrienn Kazsoki,
Benjámin Gyarmati,
András Szilágyi,
Gábor Vasvári,
Gábor Katona,
Lajos Szente,
Romána Zelkó,
László Poppe,
Diána Balogh-Weiser,
György T. Balogh
Affiliations
Gergő Dániel Tóth
Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Adrienn Kazsoki
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre utca 7-9, H-1092 Budapest, Hungary
Benjámin Gyarmati
Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
András Szilágyi
Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Gábor Vasvári
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei u. 98, H-4032 Debrecen, Hungary
Gábor Katona
Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Lajos Szente
Cyclolab Cyclodextrin Research & Development Laboratory Ltd., Illatos út 7, H-1097 Budapest, Hungary
Romána Zelkó
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre utca 7-9, H-1092 Budapest, Hungary
László Poppe
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Diána Balogh-Weiser
Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
György T. Balogh
Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
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.
