Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes.

Thuan Thi Duong,Arvo Tõnisoo,Antti Isomäki,Tran Thi Hai Yen,Ain Raal,Thi-Minh-Hue Pham,Karin Kogermann,Urve Paaver,Jyrki Heinämäki,Ivo Laidmäe

doi:10.3390/molecules26092591

Abstract

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

Highlights

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid (Figure 1)of plant origin
The size and size distribution of the liposomes were determined with two nanoparticle tracking measurement systems, Zetasizer Nano ZSP and ZetaView®
Our results showed that the BBR-loaded liposomes prepared by the ethanol-injection method are smaller in size and have a more uniform size distribution than the corresponding liposomes prepared by the thin-film hydration method (Table 1)

Summary

Introduction

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid (Figure 1)of plant origin. BBR has low oral bioavailability due to a first-pass metabolism effect in the intestinal tract, poor intestinal permeability, self-aggregation, P-glycoprotein mediated efflux and hepatobiliary re-excretion [7,8]. BBR has been shown to induce the activity of multidrug efflux transporter P-glycoprotein (P-gp) in the intestine responsible for active-efflux of drugs from cells, and less than 10% of oral BBR transports through the intestinal wall [9]. Such limitations associated with the poor oral bioavailability of BBR could be overcome by nanoformulating BBR-loaded liposomes

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Discussion

Conclusion