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@article{Anderson:2010:10.1186/ar3089,
author = {Anderson, R and Franch, A and Castell, M and Perez-Cano, FJ and Braeuer, R and Pohlers, D and Gajda, M and Siskos, AP and Katsila, T and Tamvakopoulos, C and Rauchhaus, U and Panzner, S and Kinne, RW},
doi = {10.1186/ar3089},
journal = {Arthritis Research and Therapy},
pages = {1--15},
title = {Liposomal encapsulation enhances and prolongs the anti-inflammatory effects of water-soluble dexamethasone phosphate in experimental adjuvant arthritis},
url = {http://dx.doi.org/10.1186/ar3089},
volume = {12},
year = {2010}
}

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TY  - JOUR
AB  - IntroductionThe objective of this study was to evaluate the efficacy of intravenous (i.v.) injection of liposomally encapsulated dexamethasone phosphate (DxM-P) in comparison to free DxM-P in rats with established adjuvant arthritis (AA). This study focused on polyethylene glycol (PEG)-free liposomes, to minimize known allergic reactions caused by neutral PEG-modified (PEG-ylated) liposomes.MethodsEfficacy was assessed clinically and histologically using standard scores. Non-specific and specific immune parameters were monitored. Activation of peritoneal macrophages was analyzed via cytokine profiling. Pharmacokinetics/biodistribution of DxM in plasma, synovial membrane, spleen and liver were assessed via mass spectrometry.ResultsLiposomal DxM-P (3 × 1 mg/kg body weight; administered intravenously (i.v.) on Days 14, 15 and 16 of AA) suppressed established AA, including histological signs, erythrocyte sedimentation rate, white blood cell count, circulating anti-mycobacterial IgG, and production of interleukin-1beta (IL-1β) and IL-6 by peritoneal macrophages. The suppression was strong and long-lasting. The clinical effects of liposomal DxM-P were dose-dependent for dosages between 0.01 and 1.0 mg/kg. Single administration of 1 mg/kg liposomal DxM-P and 3 × 1 mg/kg of free DxM-P showed comparable effects consisting of a partial and transient suppression. Moreover, the effects of medium-dose liposomal DxM-P (3 × 0.1 mg/kg) were equal (in the short term) or superior (in the long term) to those of high-dose free DxM-P (3 × 1 mg/kg), suggesting a potential dose reduction by a factor between 3 and 10 by liposomal encapsulation. For at least 48 hours after the last injection, the liposomal drug achieved significantly higher levels in plasma, synovial membrane, spleen and liver than the free drug.ConclusionsThis new PEG-free formulation of macrophage-targeting liposomal DxM-P considerably reduces the dose and/or frequency required to treat AA, wi
AU  - Anderson,R
AU  - Franch,A
AU  - Castell,M
AU  - Perez-Cano,FJ
AU  - Braeuer,R
AU  - Pohlers,D
AU  - Gajda,M
AU  - Siskos,AP
AU  - Katsila,T
AU  - Tamvakopoulos,C
AU  - Rauchhaus,U
AU  - Panzner,S
AU  - Kinne,RW
DO  - 10.1186/ar3089
EP  - 15
PY  - 2010///
SN  - 1478-6354
SP  - 1
TI  - Liposomal encapsulation enhances and prolongs the anti-inflammatory effects of water-soluble dexamethasone phosphate in experimental adjuvant arthritis
T2  - Arthritis Research and Therapy
UR  - http://dx.doi.org/10.1186/ar3089
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000283841500021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://arthritis-research.biomedcentral.com/articles/10.1186/ar3089
UR  - http://hdl.handle.net/10044/1/81694
VL  - 12
ER  -

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