| Niclosamide is an anthelmintics with cancer-fighting potential. It has demonstrated its great potential in fighting against leukemia cell recently. However, either oral or injections of NL is challenged by its insoluble(in water and lipid)nature.Purpose: The purpose of this study was to screen the stable and feasible formulation process of NL-loaded submicron lipid emulsions(NL-SLEs). Here we developed two different NL-SLEs and compared their suitability in bioavailability enhancement.Method: The prescription and formulation process of NL-SLEs(NL-CSLEs and NL-PSLEs) were screened using single factor design. NL-SLEs were prepared by melt dispersion/high pressure homogenization. The concentration of NL entrapped in SLEs was quantified by HPLC. NL-SLEs were characterized by particle size, in vitro release and lipolysis, mucin binding appetence and intestinal permeability. The blood from the tail of rats was drawn after administering oral medications, and HPLC was adopted to detect the NL concentrations in the blood. In this way, the pharmacokinetic parameters and bioavailability were calculated.Results: NL-CSLEs and NL-PSLEs were successfully achieved, and their quality was stable. Conventional and PEGylated NL-SLEs(NL-CSLEs and NL-PSLEs) were prepared by melt dispersion/high pressure homogenization. NL-CSLEs and NL-PSLEs were about 307.80 nm and 162.00 nm in particle size, and both of them possessed satisfactory stability and drug load(> 9.0%). After oral administration, significantly enhanced bioavailability was achieved through NL-CSLEs and NL-PSLEs(441.11% and 463.55% relative to reference, respectively). Apart from global size,NL-CSLEs and NL-PSLEs exhibited similar attributes in release, lipolysis, mucin binding, etc.Conclusion: Taken together, SLEs with or without PEG-lipid have shown to be promising for oral delivery of NL. PEG-lipid could significantly reduce the particle size of SLEs. |
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