The Effects of Primary Unconjugated Bile Acids on Nanoencapsulated Pharmaceutical Formulation of Hydrophilic Drugs: Pharmacological Implications

Abstract

Introduction

In a recent study, in our laboratory, primary unconjugated bile acids, commonly found in humans, chenodeoxycholic acid (CDCA), have been shown to improve stability of nanoencapsulated lipophilic drugs and improve their release profile after oral administration likely via electrokinetic stabilisation. Hence, this study aimed to examine the effects of CDCA on exerting similar effects on hydrophilic drugs.

Methods

Various CDCA-based formulations were produced for the orally administered hydrophilic drug, metformin. Analyses of these formulations included electrokinetic potentials, topography, drug and CDCA formulation contents, nano size distribution, heat-induced deformation and outer-core expansion indices, release profiles, shell-resistance ratio, and thermal and chemical indices. With the drug’s main target being pancreatic beta-cells, the formulations’ effects on cell viability, functions and inflammatory profiles were also investigated.

Results and Conclusions

CDCA-based metformin formulations exhibited improved stability and release profiles via thermal, chemical and electrokinetic effects, which were formulation-dependent suggesting potential applications of CDCA in the oral targeted delivery of hydrophilic drugs.

Keywords:

• microencapsulation
• diabetes mellitus
• Glyceryl monooleate
• Eudragit
• chenodeoxycholic acid

Acknowledgments

The authors acknowledge the Australian Postgraduate Award and the Curtin Research Scholarship for the support. The authors acknowledge the use of laboratory equipment, and the scientific and technical assistance of the Curtin University Electron Microscope Facility, which has been partially funded by the University, State and Commonwealth Governments. MIN-6 cells were provided by the University of Western Australia and their acquirement and use was approved by Curtin University’s institutional guidelines.

Disclosure

Hani Al-Salami reports grants from Beijing Nat-Med Biotechnology Co. Ltd, European Union Horizon 2020 research project, Curtin Faculty ORS-WAHAI Consortium, and Australian National Health and Medical Research, during the conduct of the study. Jafri Kuthubutheen, Hani Al-Salami, Armin Mooranian, and Daniel Brown report a patent Australian Provisional Patent Application No. 2020901933 “Treatment methods and formulations”. Hani Al-Salami and Armin Mooranian report a patent Encapsulation Technology in cannabinoids oral delivery. The authors report no other potential conflicts of interest for this work.

Additional information

Funding

H Al-Salami has been and is currently receiving funding from Beijing Nat-Med Biotechnology Co. Ltd. The work is partially supported by the European Union Horizon 2020 research project and innovation program under the Marie Skłodowska-Curie Grant Agreement No 872370. Curtin Faculty ORS-WAHAI Consortium and the Australian National Health and Medical Research (APP9000597).