Significantly enhanced bioavailability of niclosamide through submicron lipid emulsions with or without PEG-lipid: a comparative study

Abstract

Niclosamide (NL) has demonstrated its great potential in fighting against leukaemia recently. However, either oral or systemic delivery of NL is challenged by its insoluble nature. Here, we developed two different NL-loaded submicron lipid emulsions (NL-SLEs) and compared their suitability in bioavailability enhancement. Conventional and PEGylated NL-SLEs (NL-CSLEs and NL-PSLEs) were prepared by melt dispersion/high pressure homogenisation technique. They were about 307.8 and 162.2 nm in particle size, respectively, 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 the reference). Apart from global size, NL-CSLEs and NL-PSLEs exhibited similar attributes in release, lipolysis, mucin binding, etc. 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. But, macromolecular PEG-lipid was required to effectively stealth the lipid carriers.

• Bioavailability
• lipid-based formulation
• niclosamide
• PEGylation
• stealth

Declaration of interest

The authors declare that there are no conflicts of interest concerning this study. The authors alone are responsible for the content and writing of the paper.

This work was co-supported by the National Natural Science Foundation of China (81373496) and China Postdoctoral Science Foundation (2014M562253).