Design and evaluation of nanostructured lipid carrier of Bergenin isolated from Pentaclethra macrophylla for anti-inflammatory effect on lipopolysaccharide-induced inflammatory responses in macrophages.

Herein, we report the properties of nanostructured lipid carriers (NLCs) prepared with a gradient concentration of Bergenin (BGN) isolated from Pentaclethra macrophylla stem bark powder. A gradient concentration of BGN (BGN 0, 50, 100, 150, and 200 mg) was prepared in a 5 % lipid matrix consisting of Transcutol HP (75 %), Phospholipon 90H (15 %), and Gelucire 43/01 (10 %) to which a surfactant aqueous phase consisting of Tween 80, sorbitol, and sorbic acid was dissolved. The NLCs were evaluated by size, polydispersity index (PDI), zeta potential, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), encapsulation efficiency, and in vitro drug release. The result shows polydispersed nanoparticles with high drug encapsulation (94.26-99.50 %). The nanoparticles were mostly spherical, but those from the 50 mg BGN batch were more cuboidal than spherical. The drug release was highest from the latter to the tune of 40 % compared to the pure BGN solution, which released about 15 % BGN. The anti-inflammatory activity of the BGN-NLC and total plant extract was studied on lipopolysaccharide (LPS)-inflamed macrophages. The cell study showed that BGN and plant extract had low cytotoxicity on macrophages and exhibited a dose-dependent anti-inflammatory effect on the LPS-induced inflammatory process in macrophages.

A Monoclonal Human Alveolar Epithelial Cell Line ("Arlo") with Pronounced Barrier Function for Studying Drug Permeability and Viral Infections.

In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well as toxicological responses in humans. Models based on human cells and tissues are potential alternatives to animal experimentation allowing for the isolation of essential processes of human biology and making them accessible in vitro. Here, the generation of a novel monoclonal cell line "Arlo," derived from the polyclonal human alveolar epithelium lentivirus immortalized cell line hAELVi via single-cell printing, and its characterization as a model for the human alveolar epithelium as well as a building block for future complex in vitro models is described. "Arlo" is systematically compared in vitro to primary human alveolar epithelial cells (hAEpCs) as well as to the polyclonal hAELVi cell line. "Arlo" cells show enhanced barrier properties with high transepithelial electrical resistance (TEER) of ≈3000 Ω cm2 and a potential difference (PD) of ≈30 mV under air-liquid interface (ALI) conditions, that can be modulated. The cells grow in a polarized monolayer and express genes relevant to barrier integrity as well as homeostasis as is observed in hAEpCs. Successful productive infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a proof-of-principle study offers an additional, attractive application of "Arlo" beyond biopharmaceutical experimentation.