Jakub Sirc1, Zuzana Hampejsova2, Jana Trnovska2, Petr Kozlik2, Jakub Hrib1, Radka Hobzova1, Alena Zajicova3, Vladimir Holan3, Zuzana Bosakova4. 1. Department of Polymer Networks and Gels, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06, Prague 6, Czech Republic. 2. Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic. 3. Department of Transplantation Immunology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic. 4. Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic. bosakova@natur.cuni.cz.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Austin C Li; Yinghe Li; Micheal S Guirguis; Robert G Caldwell; Wilson Z Shou Journal: J Pharm Biomed Anal Date: 2006-08-02 Impact factor: 3.935
Authors: Michal Dubský; Sárka Kubinová; Jakub Sirc; Luděk Voska; Robert Zajíček; Alena Zajícová; Petr Lesný; Alexandra Jirkovská; Jiří Michálek; Marcela Munzarová; Vladimír Holáň; Eva Syková Journal: J Mater Sci Mater Med Date: 2012-02-14 Impact factor: 3.896
Authors: Jakub Sirc; Sarka Kubinova; Radka Hobzova; Denisa Stranska; Petr Kozlik; Zuzana Bosakova; Dana Marekova; Vladimir Holan; Eva Sykova; Jiri Michalek Journal: Int J Nanomedicine Date: 2012-10-08