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Cyclosporine A loaded electrospun poly(D,L-lactic acid)/poly(ethylene glycol) nanofibers: drug carriers utilizable in local immunosuppression
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SYSNO ASEP 0474919 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cyclosporine A loaded electrospun poly(D,L-lactic acid)/poly(ethylene glycol) nanofibers: drug carriers utilizable in local immunosuppression Author(s) Širc, Jakub (UMCH-V) RID, ORCID
Hampejsová, Z. (CZ)
Trnovská, J. (CZ)
Kozlík, P. (CZ)
Hrib, Jakub (UMCH-V) RID
Hobzová, Radka (UMCH-V) RID, ORCID
Zajícová, Alena (UEM-P) RID
Holáň, Vladimír (UEM-P) RID
Bosáková, Z. (CZ)Source Title Pharmaceutical Research. - : Springer - ISSN 0724-8741
Roč. 34, č. 7 (2017), s. 1391-1401Number of pages 11 s. Language eng - English Country US - United States Keywords cyclosporine A ; drug release kinetics ; LC-MS/MS Subject RIV CD - Macromolecular Chemistry OECD category Biochemical research methods Subject RIV - cooperation Institute of Experimental Medicine - Other Materials R&D Projects GA16-04863S GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMCH-V - RVO:61389013 ; UEM-P - RVO:68378041 UT WOS 000402193300004 EID SCOPUS 85017551870 DOI 10.1007/s11095-017-2155-x Annotation The present study aims to prepare poly(D,L-lactic acid) (PLA) nanofibers loaded by the immunosuppressant cyclosporine A (CsA, 10 wt%). Amphiphilic poly(ethylene glycol)s (PEG) additives were used to modify the hydrophobic drug release kinetics. Four types of CsA-loaded PLA nanofibrous carriers varying in the presence and molecular weight (MW) of PEG (6, 20 and 35 kDa) were prepared by needleless electrospinning. The samples were extracted for 144 h in phosphate buffer saline or tissue culture medium. A newly developed and validated LC-MS/MS method was utilized to quantify the amount of released CsA from the carriers. In vitro cell experiments were used to evaluate biological activity. Nanofibers containing 15 wt% of PEG showed improved drug release characteristics. Significantly higher release rates were achieved in initial part of experiment (24 h). The highest released doses of CsA were obtained from the nanofibers with PEG of the lowest MW (6 kDa). In vitro experiments on ConA-stimulated spleen cells revealed the biological activity of the released CsA for the whole study period of 144 h and nanofibers containing PEG with the lowest MW exhibited the highest impact (inhibition). The addition of PEG of a particular MW enables to control CsA release from PLA nanofibrous carriers. The biological activity of CsA-loaded PLA nanofibers with PEG persists even after 144 h of previous extraction. Prepared materials are promising for local immunosuppression in various medical applications. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2018
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