Surface-Modified Solid Lipid Nanoparticulate Formulation for Ifosfamide: Development and Characterization

Abstract

Aims: The present research focuses on the development of the surface modified solid lipid nanoparticulate (SLN) system for enhancing the stability and sustaining the release of a model hydrophilic drug ifosfamide. Materials & Methods: SLNs consisting of glyceryl monooleate (GMO) and chitosan were prepared by double emulsion technique, crosslinked with sodium tripolyphosphate, followed by lyophilization under two different vacuum conditions. The physicochemical characterization of SLNs included evaluation of surface morphology, particle size and surface charge, moisture content and physical state of the drug in the delivery system. The in vitro drug release and the stability were evaluated using high-performance liquid chromatography and liquid chromatography/mass spectrometry, respectively. Cellular permeability and subcellular localization studies were performed using Caco-2 cells. Results: Different chamber pressures during lyophilization produced SLNs with different morphologies and moisture contents. SLNs demonstrated high encapsulation efficiency, sustained release, and enhanced stability of ifosfamide with a high cellular uptake and permeability for Caco-2 cells. Conclusion: GMO and chitosan SLNs could be successfully used for enhancing the stability, sustaining the release, enhancing the targeting and permeability characteristics of ifosfamide.

Keywords::

• Caco-2
• chitosan
• GMO
• ifosfamide
• LC/MS
• solid lipid nanoparticles
• TPP

Financial & competing interests disclosure

These studies were funded by the School of Pharmacy and Health Sciences, Creighton University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank Richard Graves from Xavier University for his help with SEM analysis and Nitin Tayade from University of Minnesota for his help with XRD analysis. Support from Heather Jenson-Smith of Integrated Biomedical Imaging Facility, Creighton University for confocal microscopy is highly appreciated.

Additional information

Funding

These studies were funded by the School of Pharmacy and Health Sciences, Creighton University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.