Synergistic Role of Self-Emulsifying Lipids and Nanostructured Porous Silica Particles in Optimizing The Oral Delivery of Lovastatin

Abstract

Aim: To investigate the role of self-emulsifying lipids and porous silica particles in enhancing supersaturated drug loading and biopharmaceutical performance of nanostructured silica–lipid hybrid (SLH) systems. Materials & methods: Two lovastatin (LOV)-SLHs were engineered from self-emulsifying lipid (Gelucire^® 44/14; Gattefossé, Lyon, France) and Aerosil^® 380 (SLH-A; Evonik Industries, Essen, Germany) or Syloid^® 244FP silica (SLH-S; Grace Davison Discovery Sciences, Rowville, Australia). Results & discussion: The LOV-SLHs encapsulated LOV at 10% w/w, which is ≥3-fold higher than typical lipid formulations in the absence of porous silica. The LOV-SLHs retained self-emulsifying lipid-associated solubilization benefits and improved drug solubilization by twofold in simulated intestinal condition. SLH-S, with larger surface area (299 m²/g), was superior to SLH-A (184 m²/g) in optimizing oral bioavailability, suggesting a critical role of the silica geometry. Bioavailability of SLH-S was 2.8- and 1.3-fold higher than pure drug and drug suspension in Gelucire 44/14, respectively. Conclusion: In conclusion, SLHs profit from advantages associated with both self-emulsifying lipids and porous silica, and provide potentially improved therapy against coronary artery disease.

Keywords::

• bioavailability
• lovastatin
• oral delivery
• porous silica particle
• self-emulsifying lipid
• silica–lipid hybrid

Financial & competing interests disclosure

The Australian Research Council, the Australian National Health and Medical Research Council, ITEK Pty Ltd, Bioinnovation South Australia and the Australian Biotech Ceridia Pty Ltd are greatly acknowledged for research funding and support. 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 are thankful to Reid Animal Facility, University of South Australia (Adelaide, Australia), for experimental support of in vivo studies. L Waterhouse and A McFadden from Adelaide Microscopy, University of Adelaide (Australia), are acknowledged for assistance in obtaining scanning electron microscopy images and studying surface properties of silica–lipid hybrid formulations.

Additional information

Funding

The Australian Research Council, the Australian National Health and Medical Research Council, ITEK Pty Ltd, Bioinnovation South Australia and the Australian Biotech Ceridia Pty Ltd are greatly acknowledged for research funding and support. 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.