Preparation, characterization, in vitro and in vivo studies of liposomal berberine using novel natural fiber Interlaced liposomal technology

Abstract

Berberine hydrochloride (BBR), used in various traditional medicinal practices, has a variety of pharmacological effects. It is a plant-derived quaternary isoquinoline alkaloid with a low water solubility that may be used in the treatment of conditions such as hypercholesterolemia. However, the therapeutic use of BBR has been compromised because of its hydrophobic characteristics, in addition to its low stability and poor bioavailability. To overcome these drawbacks of BBR’s oral bioavailability, technologies like liposomal delivery systems have been developed to ensure enhanced absorption. But conventional liposomes have low physical and chemical stability due to delicate liposomal membranes, peroxidation and rapid clearance from the bloodstream. Surface modification of liposomes could be a solution and creating a liposome with plant-based fibers as surface material will provide enhanced stability, aqueous solubility and protection against degradation. Consequently, the aim of this study is to create and describe a Fiber Interlaced Liposome™ (FIL) as a vehicle for an enhanced bioavailability platform for BBR and other biomolecules. This optimised FIL-BBR formulation was analysed for its structural and surface morphological characteristics by using FTIR, SEM, TEM, XRD, zeta potential and DSC. Encapsulation efficiency, stability, and sustained release studies were done using an in vitro digestion model with simulated gastric and intestinal fluids. FIL formulation showed a sustained release of BBR at 59.03 % as compared to the unformulated control (46.73 %) after 8 h of dialysis. Furthermore, the FIL-BBR demonstrated enhanced stability in the simulated gastric fluid (SGF) in addition to a more sustained release in the simulated intestinal fluid (SIF). The efficacy of FIL-BBR were further anlaysed by an in vivo bioavailability study using male Wistar rats and it demonstrated a 3.37 −fold higher relative oral bioavailability compared to the unformulated BBR. The AUC 0-t for BBR in FIL-BBR was 1.38 ng.h/mL, significantly greater than the unformulated BBR (0.041 ng.h/mL). Similarly, the Cmax for BBR in FIL-BBR (50.98 ng/mL) was discovered to be far greater than unformulated BBR (15.54 ng/mL) after the oral administration. These findings imply that fiber based liposomal encapsulation improves the stability and slows down BBR release, which could be advantageous for applications requiring a higher bioavailability and a more sustained release.