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

Armin Mooranian; Thomas Foster; Corina M Ionescu; Louise Carey; Daniel Walker; Melissa Jones; Susbin Raj Wagle; Bozica Kovacevic; Jacqueline Chester; Edan Johnstone; Jafri Kuthubutheen; Daniel Brown; Marcus D Atlas; Momir Mikov; Hani Al-Salami

doi:10.2147/DDDT.S328526

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

Drug Des Devel Ther. 2021 Oct 23:15:4423-4434. doi: 10.2147/DDDT.S328526. eCollection 2021.

Authors

Armin Mooranian^{1

2}, Thomas Foster^{1

2}, Corina M Ionescu^{1

2}, Louise Carey^{1

2}, Daniel Walker^{1

2}, Melissa Jones^{1

2}, Susbin Raj Wagle^{1

2}, Bozica Kovacevic^{1

2}, Jacqueline Chester^{1

2}, Edan Johnstone^{1

2}, Jafri Kuthubutheen³, Daniel Brown⁴, Marcus D Atlas², Momir Mikov⁵, Hani Al-Salami^{1

2}

Affiliations

¹ The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, 6102, WA, Australia.
² Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, 6009, WA, Australia.
³ Fiona Stanley Hospital, Perth, WA, Australia.
⁴ Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
⁵ Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, 21101, Serbia.

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: Eudragit; Glyceryl monooleate; chenodeoxycholic acid; diabetes mellitus; microencapsulation.

MeSH terms

Administration, Oral
Animals
Cell Line
Cell Survival
Chemistry, Pharmaceutical
Chenodeoxycholic Acid / chemistry*
Drug Delivery Systems*
Drug Liberation
Drug Stability
Hydrophobic and Hydrophilic Interactions
Insulin-Secreting Cells / metabolism
Metformin / administration & dosage*
Metformin / chemistry
Mice
Nanocapsules*
Particle Size

Substances

Nanocapsules
Chenodeoxycholic Acid
Metformin

Grants and 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).