AIM: The nephrotoxicity and immunosuppressive ability of cyclosporine (CyA) incorporated into polycaprolactone nanoparticles (CyA-NP) was assessed in vitro and in vivo and compared to the effects caused by free drug (Sandimmun. METHODS: The in vivo study included four groups (12 Wistar rats each) receiving oral CyA (10 mg/kg/day for 3 days) as an emulsion of Sandimmun in whole milk or CyA-NP and equivalent doses of empty NP or cremophor in milk as controls. CyA concentrations in blood, urine, liver, spleen and kidney at 24 h post-dosing were measured by fluorescence polarization immunoassay (FPIA). The nephrotoxicity induced by each drug treatment was determined by measuring creatinine plasma levels, malonyl dialdehyde production, and H(2)O(2) and reduced glutathione contents in glomeruli. On the other hand, the immunosuppressive effect was estimated in vivo by incubating lymphocyte suspensions obtained from CyA-, CyA-NP- and control-treated rats, as well as in vitro on lymphocyte suspensions from non-treated healthy animals. RESULTS: Significantly higher blood, urine and tissue levels were achieved with CyA-NP compared to free CyA. However, no changes in creatinine plasma levels were detected due to either CyA or CyA-NP treatment. Only the production of H(2)O(2) in the glomeruli exhibited a significant increase as compared to control groups, but no differences could be ascribed to the different drug treatments. In vivo, the immunosuppressive activity was also comparable for both drug treatments. In contrast, CyA-NP showed a better drug uptake in vitro at concentrations above 25 microM. No immunosuppression was detected in control groups. CONCLUSION: NP improve the oral bioavailability of CyA and its uptake by lymphocytes in vitro above 25 microM. On the contrary, specific immunosuppression and adverse effects were not simultaneously increased. Further studies are needed to clarify the results.
AIM: The nephrotoxicity and immunosuppressive ability of cyclosporine (CyA) incorporated into polycaprolactone nanoparticles (CyA-NP) was assessed in vitro and in vivo and compared to the effects caused by free drug (Sandimmun. METHODS: The in vivo study included four groups (12 Wistar rats each) receiving oral CyA (10 mg/kg/day for 3 days) as an emulsion of Sandimmun in whole milk or CyA-NP and equivalent doses of empty NP or cremophor in milk as controls. CyA concentrations in blood, urine, liver, spleen and kidney at 24 h post-dosing were measured by fluorescence polarization immunoassay (FPIA). The nephrotoxicity induced by each drug treatment was determined by measuring creatinine plasma levels, malonyl dialdehyde production, and H(2)O(2) and reduced glutathione contents in glomeruli. On the other hand, the immunosuppressive effect was estimated in vivo by incubating lymphocyte suspensions obtained from CyA-, CyA-NP- and control-treated rats, as well as in vitro on lymphocyte suspensions from non-treated healthy animals. RESULTS: Significantly higher blood, urine and tissue levels were achieved with CyA-NP compared to free CyA. However, no changes in creatinine plasma levels were detected due to either CyA or CyA-NP treatment. Only the production of H(2)O(2) in the glomeruli exhibited a significant increase as compared to control groups, but no differences could be ascribed to the different drug treatments. In vivo, the immunosuppressive activity was also comparable for both drug treatments. In contrast, CyA-NP showed a better drug uptake in vitro at concentrations above 25 microM. No immunosuppression was detected in control groups. CONCLUSION: NP improve the oral bioavailability of CyA and its uptake by lymphocytes in vitro above 25 microM. On the contrary, specific immunosuppression and adverse effects were not simultaneously increased. Further studies are needed to clarify the results.
Authors: Huanyu Dou; Christopher J Destache; Justin R Morehead; R Lee Mosley; Michael D Boska; Jeffrey Kingsley; Santhi Gorantla; Larisa Poluektova; Jay A Nelson; Mahesh Chaubal; Jane Werling; James Kipp; Barrett E Rabinow; Howard E Gendelman Journal: Blood Date: 2006-06-29 Impact factor: 22.113
Authors: Huanyu Dou; Cassi B Grotepas; JoEllyn M McMillan; Christopher J Destache; Mahesh Chaubal; Jane Werling; James Kipp; Barrett Rabinow; Howard E Gendelman Journal: J Immunol Date: 2009-06-17 Impact factor: 5.422
Authors: Katarzyna Jelonek; Janusz Kasperczyk; Suming Li; Piotr Dobrzynski; Henryk Janeczek; Bozena Jarzabek Journal: Biomed Res Int Date: 2013-10-28 Impact factor: 3.411