A liposome-micelle-hybrid (LMH) oral delivery system for poorly water-soluble drugs: Enhancing solubilisation and intestinal transport

Bilquis Romana; Md Musfizur Hassan; Fabio Sonvico; Gabriela Garrastazu Pereira; Alex F Mason; Pall Thordarson; Kristen E Bremmell; Timothy J Barnes; Clive A Prestidge

doi:10.1016/j.ejpb.2020.07.022

A liposome-micelle-hybrid (LMH) oral delivery system for poorly water-soluble drugs: Enhancing solubilisation and intestinal transport

Eur J Pharm Biopharm. 2020 Sep:154:338-347. doi: 10.1016/j.ejpb.2020.07.022. Epub 2020 Jul 31.

Authors

Bilquis Romana¹, Md Musfizur Hassan², Fabio Sonvico³, Gabriela Garrastazu Pereira³, Alex F Mason², Pall Thordarson², Kristen E Bremmell⁴, Timothy J Barnes⁴, Clive A Prestidge⁵

Affiliations

¹ School of Chemistry, The Australian Centre for Nanomedicine and The ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia; University of South Australia, Clinical and Health Sciences, Adelaide, South Australia 5000, Australia.
² School of Chemistry, The Australian Centre for Nanomedicine and The ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia.
³ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia.
⁴ University of South Australia, Clinical and Health Sciences, Adelaide, South Australia 5000, Australia.
⁵ University of South Australia, Clinical and Health Sciences, Adelaide, South Australia 5000, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Mawson Lakes 5095, Australia. Electronic address: clive.prestidge@unisa.edu.au.

PMID: 32739535
DOI: 10.1016/j.ejpb.2020.07.022

Abstract

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption.

Keywords: Bioavailability; Caco-2 cells; LMH; Liposomes; Lovastatin; Micelles; P-gp; Permeability.

MeSH terms

Administration, Oral
Caco-2 Cells
Cell Survival / drug effects
Cell Survival / physiology
Drug Delivery Systems / methods*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism
Intestinal Absorption / drug effects
Intestinal Absorption / physiology*
Liposomes
Lovastatin / administration & dosage*
Lovastatin / metabolism*
Micelles*
Solubility / drug effects
Water / metabolism*

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Liposomes
Micelles
Water
Lovastatin