Berberine-loaded Nano-Liposomes Generated with Ethanol-Injection and Thin-film Hydration Methods

Abstract

The poor solubility in water is very often a problem for active pharmaceutical substances of plant origin. The formulation of such drugs as liposomal preparations enables to improve the bioavailability of these drugs. Berberine (BBR) is a quaternary isoquinoline alkaloid derived from many native plant species (Coptis spp., Berberis spp., Hydrastis canadensis etc.). BBR has been traditionally used for the treatment of different disorders including hyper-cholesterolemia and cardiovascular diseases [1,2]. BBR has a strong antimicrobial activity enabling the use of it as an anti-diarrheal, anti-protozoal, fungal, candida, yeast, and parasitic intestinal active ingredient [3]. In addition, BBR has shown an anti-inflammatory, anti-diabetic, lipid peroxidation, and neuroprotective activity [3,4]. Unfortunaterly, BBR is poorly soluble in water and has a low bioavailability (<10%) due to the induced activity of multidrug efflux transporter Pglycoprotein (P-gp) in the intestine itself [2]. Such limitations associated with a poor oral bioavailability of BBR could be overcome by nanoformulating BBR to liposomes. Pharmaceutical liposomes can be fabricated by ethanol-injection and thin-film hydration methods. The lamellarity, size, shape and ultra-structure of liposomes can be determined by using different advanced techniques, such as cryogenic electron microscopy (Cryo-EM), dynamic light scattering (DLS), size-exclusion chromatography (SEC), and atomic force microscopy (AFM) [5]. Confocal laser scanning microscopy (CLSM) has been also used for such imaging [6]. The aim of our study is to investigate ethanolinjection and film hydration methods for generating BBR-loaded liposomes and to study the structure, size, size distribution and entrapment efficiency of the liposomes. The liposomes are ultimately intended for the oral treatment of hypercholesterolemia.