Peptide and protein drugs have grown to be the new era of therapeutics, yet many of them are just available as shots, and reviews on oral community intestinal delivery of peptides and proteins are very limited. microemulsion had been orally gavaged to mice. The half-existence of TAMRA-TAT in microemulsion was improved nearly three-fold in comparison to that in the drinking water remedy when challenged by MSIF. The procedure with TAMRA-TAT microemulsion after oral administration led to greater fluorescence strength in every intestine sections (duodenum, jejunum, ileum, and colon) in comparison to TAMRA-TAT remedy or placebo microemulsion. The and research collectively suggested TAMRA-TAT Taxol was better shielded in the w/o microemulsion within an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration. and to inhibit activated NF-B, a hallmark of chronic inflammation, but not Taxol basal NF-B activity, and ameliorated intestinal inflammation in experimental IBD models (17). The selective targeting of 8K-NBD to activated NF-B makes it an excellent therapeutic candidate and our research interest. However, a significant challenge for oral delivery of 8K-NBD is its chemical and biological degradation in the gastrointestinal tract. To address this issue and deliver 8K-NBD or other water-soluble peptides locally to the inflamed intestine, the peptide will be incorporated into w/o microemulsions, which will be followed by incorporating the optimal w/o microemulsion into enteric-coated hard gelatin capsules to further enhance local peptide delivery in the GI where needed. The current work is to test the first part of the hypothesis that w/o microemulsions may provide protection to the peptide incorporated when challenged and and The shear viscosity of the w/o microemulsions was measured using a Brookfield LVDV-III + Cone and Plate Rheometer (Brookfield Engineering Laboratories, Inc., Middleboro, MA, USA). The temperature was controlled by coupling to a Brookfield TC-500 Refrigerated Bath. Instrument calibration was performed using Brookfield silicone viscosity standards. A CPE Taxol 40 spindle was utilized for sample measurements. The shear stress, shear rate, and viscosity of a series of representative microemulsion samples in the microemulsion window of interest were measured. The relationship of shear stress (dynes per square centimeter) shear rate (per second) was utilized to assess the Taxol microemulsion flow behavior. The droplet diameter of the microemulsion was measured by photon correlation spectroscopy using a Zetasizer Nano ZS (Malvern Instruments Inc., Worcestershire, UK) by backscattering at a Taxol fixed angle COL27A1 of 173 at 25C. All the samples were measured in triplicates without any dilution. The conductivity of the microemulsions was measured using YSI 3200 conductivity meter (Yellow Spring Instruments Co. Inc., Yellow Springs, OH, USA) coupled to YSI 3252 dip cell with a cell constant of 1 1.0?cm?1. The instrument was calibrated using YSI conductivity calibrators. Samples were measured at ambient temperature. The morphology of the w/o microemulsion was characterized by examination of freeze fracture replicas using transmission electron microscopy (TEM). A tiny drop of microemulsion was sandwiched between gold double-replica mounts and frozen in liquid nitrogen-cooled Freon. Next, the specimens were fractured in a Balzers BAF 400T freeze fracture device at a stage temperature of ?100C under vacuum. The fractured surfaces were shadowed unidirectionally with evaporated platinum and stabilized by carbon evaporation. The resulting replicas and sample residues were rinsed in distilled water, followed by washing in a solution of 5% sodium dichromate in 50% sulfuric acid. Replicas were then transferred to distilled water, placed onto standard copper microscopy grids, examined, and photographed with a Zeiss EM 900 Transmission Electron Microscope at an accelerating voltage of 60?kV (Carl Zeiss, Thornwood, NY, USA). Phase Inversion Behavior of W/O Microemulsions To investigate the phase inversion behavior of w/o microemulsions upon dilution, a lipophilic fluorescent marker BODIPY FL C12 was incorporated into a selected w/o microemulsion at the concentration of 0.1% by weight, followed by dilutions of 2-, 5-, 10-, 50-, and 250-fold by weight with water. The w/o microemulsion with BODIPY FL C12 before and after dilution were examined under a Nikon Eclipse TE 300 Fluorescence Microscope (Fryer Co. Inc., Huntley, IL, USA). The structure of the diluted sample was further investigated by TEM. The w/o microemulsion after a ten-fold dilution in water was negatively stained as follows: a drop of diluted microemulsion in water was placed on a copper grid, followed by removal of excess sample with.