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Budavári Bálint
Development of liposomal corticosteroids

Aug 30 - szerda

09:40 – 09:55

Membránok és membránfehérjék biofizikája

E23

Development of liposomal corticosteroids

Bálint Budavári¹, Áron Karancsi¹, Balázs Gábor Pinke², Éva Pállinger³, Krisztina Juriga-Tóth¹, Márton Király⁴, Zsófia Szász³, István Voszka⁵, Kolos Molnár², László Kőhidai³, Angela Jedlovszky-Hajdu¹, Krisztina S. Nagy¹

¹Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4., H-1089 Budapest, Hungary

²Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3-9., H-1111, Budapest, Hungary

³Department of Genetics, Cell- and Immunobiology, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., H-1089 Budapest, Hungary

⁴Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, Hőgyes Endre u. 7., H-1092 Budapest, Hungary

⁵Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 37-47., H-1094 Budapest, Hungary

Introduction Liposomes are nanoscale drug delivery systems that offer many pharmacokinetic advantages. Corticosteroids as lipophilic active agents integrate into the lipid bilayer. This novel approach can improve the efficacy of several anti-inflammatory therapies.

Aims Our goals were to create long-term stable liposomes, which can incorporate and release corticosteroids at inflamed body temperature. Considering the possible future application in asthma therapy, we also aimed at reaching high entrapment efficacy (EE%) and slight drug leakage of the vesicles.

Methods 2 kinds of liposomes were prepared from 3 different phospholipids by thin layer hydration method and subsequent extrusion to get small unilamellar vesicles (SUVs). Prednisolone (Pred) and budesonide (Bud) were used as active agents. Stability tests were executed by dynamic light scattering while EE% was determined by size-exclusion gel chromatography. The effect of liposomal drugs on cell viability was measured on EBC-1 human lung carcinoma cells. The internalization of the liposomes was studied by flow cytometry (FC) and confocal microscopy (CM).

Results SUVs with 100 nm in diameter were successfully prepared. Their hydrodynamic diameter has remained in the desired range through 6 months in case of the vast majority of the samples. It turned out that the presence of corticosteroid has a bigger impact on stability, than its type. The EE% was exceptionally high in both cases (above 90%) and the drug leakage was 35-40% for Pred and 6-8% for Bud in the first 30 min. Neither the free corticosteroids nor their liposomal form affected significantly the cell viability. CM images and FC results proved equally the internalization of the vesicles by the cells.

Conclusion We have successfully created corticosteroid-loaded liposomes with long-term stability and excellent EE% due to the lipophilic character of the applied drugs. Furthermore, they are not toxic and can be internalized by the investigated pulmonary cells.

Acknowledgment

NKFIH FK 137749, NKFIH FK 138501, Semmelweis 250+ Excellence PhD Scholarship, EFOP-3.6.3-VEKOP-16-2017-00009, TKP2021-EGA-23, TKP2021-EGA-24, TKP2021-EGA/TKP2021-NVA/TKP2021-NKTA