Abstract | PURPOSE: 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 |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 24
Issue 5
Pg. 946-54
(May 2007)
ISSN: 0724-8741 [Print] United States |
PMID | 17372685
(Publication Type: Journal Article)
|
Chemical References |
- 3,5-dipentadecyloxybenzamidine hydrochloride
- Benzamidines
- Fatty Acids
- Liposomes
- prednisolone phosphate
- Prednisolone
|
Topics |
- 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
|