Enhanced Iron Removal in Experimental Iron Overload by Nanoniosomes of Desferrioxamine

Abstract

This preliminary study explores the feasibility of employing nanocapsules prepared from nonionic surfactant vesicles (niosomes) as a carrier for an iron-chelating agent, Desferrioxamine (DFO, Desferal), to enhance iron excretion from the body. The methodology consisted of creating an iron overload model in an experimental animal  followed by measurement of iron excretion pattern in the urine by atomic absorption spectrophotometry. Niosomes were prepared with span 60: cholesterol:dicetyl phosphate by the lipid hydration method with an aqueous solution of desferal. The niosome suspension was probe-sonicated and the unilamellar vesicles were separated by gel filtration chromatography on Sephadex G-50. The stability of the niosomes was determined by the degree of leakage of desferal from the vesicles at room temperature and at 4 °C. The niosomal preparation was administered subcutaneously to iron- overloaded rat kept in metabolic cages and urine was analyzed for iron content. Sections of liver, heart, kidney of control and test animals were stained with Perl stain followed by microscopic examination to grade the extent of iron accumulation. The mean size of multilamellar vesicles (MLV) before sonication was 363 ± 25 nm and that of small unilamellar vesicles (SUV) was 104 ± 3.5 nm. Percent encapsulation in SUV and MLV was 7.31 ± 0.24% and 17.27 ± 0.62% respectively. The degree of leakage of the drug from SUV stored at room temperature for 3, 7 and 28 days was 7.2 ± 0.6, 21.9 ± 2.4 and 54.0 ± 1.5% respectively and at 4 °C for corresponding periods was 4.4 ± 0.14, 17.3  ± 2.3 and 30.4 ± 1.8% respectively. The degree of leakage from MLV stored at room temperature for 3, 7 and 28 days was 8.7 ± 1.3, 15.3 ± 2.3 and 33.8 ± 1.4% respectively and at 4 °C was 2.9 ± 0.6, 9.2 ± 0.8 and 21.0 ± 0.2% respectively. The iron burden in the liver was significantly reduced by treatment with SUV and MLV. The SUV group had a mean iron content of 17.5 ± 2.3 μg/g liver tissue and the MLV group 86.5 ± 4.0 μg/g. Microscopic examination of sections of liver, heart and kidney before and after treatment with niosomes also showed significant difference in iron deposits. Urinary excretion studies revealed that the SUV group excreted iron 75 times more than the control, 4.6 times more than DFO, 8 times more than MLV and 7 times more than a mixture of free and encapsulated DFO during treatment. Encapsulation of Desferrioxamine in nanosized niosomes enhanced iron excretion in the urine compared to the free drug. Small unilamellar vesicles were more effective than multilamelllar vesicles in iron removal.

Keywords: Niosomes, desferal, iron chelator, nanocapsules, iron overload, surfactant vesicles, desferrioxamine