Berberine-loaded liposomes for oral delivery: Preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model.

Berberine (BBR) is a plant-origin quaternary isoquinoline alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects. The aim of this study was to design and generate BBR-loaded proliposomes (PLs) as solid templates for high-dose liposomes and consequently, to enhance the oral bioavailability and therapeutic effect of BBR. An air-suspension coating (layering) method was used for generating BBR-loaded PLs. The size, distribution size, morphology, and entrapment efficiency (EE) of the final reconstituted liposomes were assessed. The oral bioavailability and endogenous cholesterol lowering effects of BBR loaded in liposomes were investigated in rats and mice, respectively. The BBR-loaded PLs showed a smooth BBR-embedded film around micron-scale carrier particles (mannitol). The reconstituted BBR-loaded liposomes had a nano-scale average size (116.6 ± 5.8 nm), narrow size distribution (polydispersity index, PDI 0.269 ± 0.038), and high EE (87.8 ± 1.0%). The oral bioavailability of reconstituted BBR-loaded liposomes at a dose of 100 mg/kg in rats was increased even 628% compared to that obtained with pure BBR (according to 90% confidence interval). The BBR-loaded liposomes at the daily oral dose 100 mg/kg in P-407- reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice by 15.8%, 38.2%, and 57.0%, respectively.

Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes.

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.

An overview on keratinocyte growth factor: from the molecular properties to clinical applications.

KGF (Keratinocyte Growth Factor), also known as FGF7, is a potent mitogen for different types of epithelial cells, which regulates migration and differentiation of these cells and protects them from various insults under stress conditions. KGF is produced by mesenchymal cells and exerts its biological effects via binding to its high-affinity receptor, a splice variant of FGF receptor 2 (FGFR2-IIIb), which is expressed by various types of epithelial cells, including epidermal keratinocytes, intestinal epithelial cells, and hepatocytes. This expression pattern of KGF and its receptor suggests that KGF acts predominantly in a paracrine manner. After acute injury, in various tissues--including the skin, the bladder as well as in chronically injured tissue--KGF expression is strongly up-regulated. This up-regulation is likely to be important for the healing of injured epithelia. In addition, KGF could also exert a protective effect on these cells. There are many researches have been underway to identify clinical applications for KGF. Specifically, KGF is currently being evaluated in clinical trials sponsored by Amgen (Thousand Oaks, CA) to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In this paper, we provide an overview of the knowledge on molecular properties, biological functions and the recent findings on clinical application of KGF.