Document Detail


Advances in targeting drug delivery to glomerular mesangial cells by long circulating cationic liposomes for the treatment of glomerulonephritis.
MedLine Citation:
PMID:  17372685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Newly designed polyethylene glycol (PEG)-modified cationic liposomes, containing a novel cationic lipid TRX-20 (3,5-dipentadecyloxybenzamidine hydrochloride), bind specifically to cultured human mesangial cells, and not to endothelial cells. In this study, we investigated targeting the delivery of PEG-modified liposomes containing TRX-20 (TRX-liposomes) to mesangial cells and evaluated their pharmacokinetic behavior in a rat experimental glomerulonephritis model, using prednisolone phosphate (PSLP) as a model drug. MATERIAL AND METHODS: TRX-liposomes were injected intravenously into experimental glomerulonephritic rats and normal rats to compare its pharmacokinetic behavior with that of non-cationic liposomes (PEG-liposomes). Rhodamine-labeled liposomes were used to evaluate the accumulation in inflamed kidneys. Pharmacological effects of three formulations of PSLP (i.e., a single injection of two liposomal formulations and daily injections of PSLP in saline solution) were estimated in terms of suppressing glomerular cell proliferation in the rat nephritis model. RESULTS: TRX-liposomes markedly accumulated in the glomeruli of inflamed kidneys, but did not accumulate in the glomeruli of normal kidneys. Although the PEG-liposomes also accumulated in the glomeruli of the inflamed kidneys, their pharmacological behavior was quite different from that of the TRX-liposomes, which were internalized by the target cells. In a comparison among the three formulations of PSLP, the dose of TRX-liposomes required for significant suppression of glomerular cell proliferation was much less (dose of 0.032 mg/kg and above) than that required for the same effect by the PSLP saline solution (3.2 mg/kg daily; 12.8 mg/kg total) and PEG-liposomes (0.32 mg/kg). Interestingly, significant suppression of mesangial cell activation, as assessed by the expression of alpha-smooth muscle actin, was observed in nephritic rats treated with TRX-liposomes, but not in the other two treatment groups. CONCLUSIONS: The pharmaceutical properties of TRX-liposomes due to their preferential binding to mesangial cells and long circulation time make this a likely candidate system for targeted drug delivery to the inflamed glomeruli of glomerulonephritis.
Authors:
Katsumi Morimoto; Masayo Kondo; Kazuo Kawahara; Hideto Ushijima; Yasuhiko Tomino; Masaharu Miyajima; Junji Kimura
Related Documents :
10823185 - Comparative efficacy of fluconazole and amphotericin b in the parenteral treatment of e...
2311205 - Improved biological properties of synthetic distearoyl phosphatidyl choline-based lipos...
11158765 - Comparative toxicities and pharmacokinetics of intrathecal lipid (amphotericin b colloi...
11442275 - Lyophilized lecithin based oil-water microemulsions as a new and low toxic delivery sys...
17929705 - Anaesthesia for castration of piglets: comparison between intranasal and intramuscular ...
20622365 - Dosimetric verification of brain and head and neck intensity-modulated radiation therap...
Publication Detail:
Type:  Journal Article     Date:  2007-03-20
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-26     Completed Date:  2007-10-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  946-54     Citation Subset:  IM    
Affiliation:
Research and Development Center, Terumo co., 1500 Inokuchi, Ashigarakami-gun, Kanagawa, 259-0151, Japan. Katsumi_Morimoto@terumo.co.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Benzamidines / administration & dosage*,  chemistry,  pharmacokinetics
Cell Proliferation / drug effects
Cells, Cultured
Disease Models, Animal
Drug Delivery Systems / methods*
Drug Evaluation, Preclinical / methods
Fatty Acids / administration & dosage*,  chemistry,  pharmacokinetics
Glomerulonephritis / drug therapy*,  metabolism,  pathology
Injections, Intravenous
Liposomes / chemistry
Male
Mesangial Cells / drug effects*,  metabolism,  pathology
Microscopy, Fluorescence
Molecular Structure
Prednisolone / administration & dosage,  analogs & derivatives,  pharmacokinetics,  therapeutic use
Rats
Rats, Sprague-Dawley
Tissue Distribution
Chemical
Reg. No./Substance:
0/3,5-dipentadecyloxybenzamidine hydrochloride; 0/Benzamidines; 0/Fatty Acids; 0/Liposomes; 302-25-0/prednisolone phosphate; 50-24-8/Prednisolone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Modified paclitaxel-loaded nanoparticles for inhibition of hyperplasia in a rabbit arterial balloon ...
Next Document:  Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension ...