TY - JOUR
T1 - In vitro evaluation of liposomal cyclosporine
AU - Vadiei, Kiumars
AU - Lopez-Berestein, Gabriel
AU - Perez-Soler, Roman
AU - Luke, David R.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1989/12/22
Y1 - 1989/12/22
N2 - The commercially available intravenous formulation of cyclosporine (CSA) is associated with acute hemodynamic changes, resulting in significant renal dysfunction. The present study investigated the properties of two liposomal CSA formulations: dimyristoylphosphatidylcholine (DMPC): stearylamine 7:1 (A) and DMPC: dimyristoylphosphatidylglycerol (DMPG) 4:1 molar ratio (B) developed as an alternative for the i.v. CSA. The optimal drug: lipid weight ratio was 1:20 for both formulations. The liposomal suspensions were obtained by rehydrating the lyophilized powder containing CSA and the lipids with saline. CSA entrapment was 90-95% for both formulations. The encapsulation efficiency of the lyophilized powder stored at 2-5°C was 95% at 24 h and not significantly different with either formulation. The encapsulation efficiency of liposomal formulations A and B in saline was 99 ± 1 and 50 ± 1%, respectively, after 5 days. In 50% serum, the encapsulation efficiency measured as percentage drug remaining entrapped at different time points was 90 ± 3 and 53 ± 4% for A and B, respectively, at 24 h. In vitro activity of both liposomal formulations demonstrated greater potency compared to the commercially available CSA i.v. formulation (A, 69.3 ± 14.8%; B, 50.8 ± 11.5%; i.v., 27.4 ± 20.6% inhibition of T-lymphocyte proliferation; p < 0.05 at 10-3 mM). The present study shows that liposomes can be used as a drug delivery system for CSA and result in an enhanced in vitro immunosuppressive potency compared with the i.v. formulation.
AB - The commercially available intravenous formulation of cyclosporine (CSA) is associated with acute hemodynamic changes, resulting in significant renal dysfunction. The present study investigated the properties of two liposomal CSA formulations: dimyristoylphosphatidylcholine (DMPC): stearylamine 7:1 (A) and DMPC: dimyristoylphosphatidylglycerol (DMPG) 4:1 molar ratio (B) developed as an alternative for the i.v. CSA. The optimal drug: lipid weight ratio was 1:20 for both formulations. The liposomal suspensions were obtained by rehydrating the lyophilized powder containing CSA and the lipids with saline. CSA entrapment was 90-95% for both formulations. The encapsulation efficiency of the lyophilized powder stored at 2-5°C was 95% at 24 h and not significantly different with either formulation. The encapsulation efficiency of liposomal formulations A and B in saline was 99 ± 1 and 50 ± 1%, respectively, after 5 days. In 50% serum, the encapsulation efficiency measured as percentage drug remaining entrapped at different time points was 90 ± 3 and 53 ± 4% for A and B, respectively, at 24 h. In vitro activity of both liposomal formulations demonstrated greater potency compared to the commercially available CSA i.v. formulation (A, 69.3 ± 14.8%; B, 50.8 ± 11.5%; i.v., 27.4 ± 20.6% inhibition of T-lymphocyte proliferation; p < 0.05 at 10-3 mM). The present study shows that liposomes can be used as a drug delivery system for CSA and result in an enhanced in vitro immunosuppressive potency compared with the i.v. formulation.
KW - Cyclosporine
KW - Intravenous formulation
KW - Liposomes
KW - T-lymphocyte proliferation
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U2 - 10.1016/0378-5173(89)90301-3
DO - 10.1016/0378-5173(89)90301-3
M3 - Article
AN - SCOPUS:0024822346
SN - 0378-5173
VL - 57
SP - 133
EP - 138
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 2
ER -