Intestinal Sacs Research Articles

Effect of Scomberomorus niphonius peptide on the characteristics of resveratrol.

Resveratrol has a variety of physiological activities, but its bioavailability in the body is low. In this study, the interaction between the peptide SH, prepared from Scomberomorus niphonius, and resveratrol was judged by fluorescence spectroscopy. Then, SHa1 was obtained by the purification of SH, and its effect on the characteristics of resveratrol was studied. SHa1 interacted with resveratrol at 37 °C for 30 min to obtain the complex SHa1-R, which then showed an obviously stronger inhibition on B16 cells than resveratrol using the MTT assay after in vitro gastrointestinal digestion. The solubility and digestive stability of SHa1-R were higher than that of free resveratrol. The intestinal absorption rate of SHa1-R was also increased compared with resveratrol according to the non-inverted rat intestinal sac model. The structure of SHa1 was analyzed by UPLC, auto amino acid analysis, and UPLC-MS/MS. The molecular weight of SHa1 was mainly concentrated under 1000 Da, and it was rich in glutamic acid, aspartic acid, lysine, and leucine. Eighteen possible peptides were identified from SHa1. The results suggested that the peptide SHa-1 may help to increase the bioavailability of resveratrol by increasing the solubility, digestive stability and intestinal absorption of resveratrol, thereby promoting its inhibitory effect on B16 cells.

Formulation and Evaluation of Dolutegravir Proliposomal Powder for Pediatric HIV Patients

Objectives: The objective of the present study was to improve the absorption of dolutegravir sodium by developing oral proliposomal formulation. Methods: Proliposomal formulations were prepared by film deposition on carrier method using cholesterol along with various lipids and different carriers. Three factors (independent variables) such as different lipids (X1), different carriers (X2) and different ratio of lipid: cholesterol (X3) were studied at all three levels, while % entrapment efficiency (%EE) (Y) was taken as the response (dependent variable). The proliposomes were optimized by Taguchi OA (L9) experimental design using Minitab 18 English software. Results and Discussion: Proliposomes were evaluated and the % EE of optimized proliposomal formulation (PL7) found to be 84.02 %. In vitro drug release was performed in 0.1N HCl and in 6.8 pH phosphate buffer with SLS using USP type II dissolution apparatus, the % drug release found to be 12.71 % in 120 min. and 98.95% in 80 min. respectively, which indicates the drug is not released in acidic medium. Surface morphology was coarse, non-porous and irregular in shape, hydration is rapid and complete conversion of proliposomes to liposomes vesicles within 2-3 min. The mean particle size is 276.6 nm, polydispersity index is 0.329 and zeta potential is -9.54 mV, may prevent aggregation of vesicles and formulation is stable. Ex-vivo absorption studies were done using the rat non-everted intestinal sac model, permeation studies revealed that Papp of the optimized proliposomal formulation and IR tablet found to be 1.19 and 0.995 cm/sec respectively indicates enhanced absorption than the pure IR tablet. Conclusion: The proliposomal formulation indicated a stable formulation with significant improvement in absorption of dolutegravir sodium.

Interaction between curcumin and a peptide and their protective effects against hepatic steatosis in mice

Curcumin is antioxidative, liver protective and it has lipid regulatory effects. However, its in vivo efficiency is limited because of the low absorption rate and bioavailability. LVYP (Leu-Val-Tyr-Pro) is a tetrapeptide isolated, purified and identified from Corbicula fluminea with strong antioxidant activity. The interaction mechanisms between curcumin and LVYP were investigated using UV–vis absorption and fluorescence spectra. The results showed that the interaction between curcumin and LVYP was hydrophobic. When the temperature was increased from 25 to 37 °C, ΔG decreased and the number of ligand molecules increased, the interaction was quenched statically explained the formation of some compounds. On the other hand, dynamic quenching occurred when the temperature reached 60 °C, ΔG increased and the number of ligand molecules decreased, which indicated that temperature affected the interaction between curcumin and LVYP. This study also showed that LVYP could promote intestinal absorption of curcumin, predominantly in the ileum, which was explored using a non-everted intestinal sac model. In vivo experiments showed that the liver's protective effect with the combined administration of LVYP and curcumin was better than the curcumin alone, and LVYP could promote the hepatoprotective function of curcumin. It was hypothesized that the interaction of LVYP and curcumin enhanced the intestinal absorption rate of curcumin, thereby increasing its liver protection effect.

Formulation and evaluation of self-nanoemulsifying drug delivery system of brigatinib: Improvement of solubility, in vitro release, ex-vivo permeation and anticancer activity

The aim of this study was to develop a novel self-nanoemulsifying drug delivery system (SNEDDS) of brigatinib, a poorly soluble anticancer drug, so as to improve its solubility, in vitro release, ex-vivo permeation and anticancer activity. Components of SNEDDS were screened on the basis of maximum solubility of brigatinib. Oleic acid, Tween 20 & diethylene glycol monoethylether were selected as oil phase, emulsifier and co-solvent respectively. Various brigatinib-SNEDDS were developed by spontaneous, low energy, simple mixing method. Developed SNEDDS were optimized on the basis of self-emulsifying capacity, globule size, size distribution, thermodynamic stability and capacity to solubilize maximum amount of brigatinib. The optimized SNEDDS was characterized for physicochemical evaluations such as viscosity, conductivity, pH and refractive index in addition to morphological evaluation of globule size and shape by transmission electron microscopy. The optimized SNEDDS exhibited approximately 205-fold enhancement in the saturation solubility of the brigatinib that resulted in improved in vitro release of drug from SNEDDS as compared to pure drug (P < 0.01). The ex-vivo permeation of brigatinib-SNEDDS across rat intestinal sacs was also improved as compared to pure drug (P < 0.01). The cytotoxic activity of brigatinib-SNEDDS against A549 human lung cancer cell lines during MTT assay were significantly improved as compared to pure brigatinib probably due to improved permeability of the SNEDD loaded brigatinib.

PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease.

Coeliac disease (CD) is a chronic, immune-mediated small intestinal enteropathy, accompanied with gluten-triggered oxidative damage of duodenal mucosa. Previously, our research group reported an increased mucosal level of the antioxidant protein Parkinson's disease 7 (PARK7) in children with CD. In the present study, we investigated the role of increased PARK7 level on the epithelial cell and mucosal integrity of the small intestine. The presence of PARK7 was investigated using immunofluorescent staining on duodenal mucosa of children with CD and on FHs74Int duodenal epithelial cells. To investigate the role of oxidative stress, FHs74Int cells were treated with H2O2 in the absence or presence of Comp23, a PARK7-binding compound. Intracellular accumulation of reactive oxygen species (ROS) was determined by DCFDA-based assay. Cell viability was measured by MTT, LDH, and Annexin V apoptosis assays. Disruption of cytoskeleton and cell adhesion was investigated by immunofluorescence staining and by real-time RT PCR. Effect of PARK7 on mucosal permeability was investigated ex vivo using intestinal sacs derived from control and Comp-23-pretreated mice. Comp23 treatment reduced the H2O2-induced intracellular accumulation of ROS, thus preserving the integrity of the cytoskeleton and also the viability of the FHs74Int cells. Accordingly, Comp23 treatment increased the expression of antioxidants (NRF2, TRX1, GCLC, HMOX1, NQO1), cell-cycle regulators (TP53, CDKN1A, PCNA, BCL2, BAX), and cell adhesion molecules (ZO1, CDH1, VCL, ITGB5) of H2O2-treated cells. Pretreatment with Comp23 considerably decreased the small intestinal permeability. In this study, we demonstrate that PARK7-binding Comp23 reduces the oxidative damage of duodenal epithelial cells, via increased expression of NRF2- and P53-regulated genes. Our results suggest that PARK7 plays a significant role in the maintenance of mucosal integrity in CD.

Effect of Baizhu (Rhizoma Atractylodis Macrocephalae) extract on intestinal absorption of brucine and strychnine in vitro and in situ.

To investigate the antagonistic effect of the extract of Baizhu (Rhizoma Atractylodis Macrocephalae) (RAM) on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica (NUX) and propose the mechanism of these effects. The apparent permeability value (Papp) and absorption rate constant (Ka) were chosen as indices. The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine. To confirm the results, the brucine and strychnine concentrations in hepatic portal venous blood were determined. Western blotting was used to study P-glycoprotein (P-gp) expression in the Caco-2 cell line. Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor, but no significant increase was noted in the presence of a tight junction regulator. The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression. The primary absorption mechanism for brucine and strychnine is passive transport, which is affected by P-gp.

Enhanced Solubility and Permeability of Naringenin Across Non-Everted Sacs of Rat Small Intestine by Lipid Nanocapsules

Naringenin (NRG) has many health benefits, including; anti-atherogenic, antiinflammatory, antitumor, and anticancer activity, as well as improvement of lipid metabolism. However, its use is limited due to its low solubility and bioavailability. The aim of the present patent study was the preparation and optimization of NRG loaded Novel Lipid Nanocapsules (LNCs) for the improvement of NRG solubility and gut permeability. Studied variables included; Solutol® HS15 and NRG concentration and the ratio of cold diluent water to primary emulsion. The storage stability of the LNCs was evaluated for 32 days and thermal analyses were conducted by Differential Scanning Calorimetry (DSC). The antioxidant properties of the NRG in LNCs were studied by measuring the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity. The enhancement of permeation of NRG by the LNCs from the intestine was evaluated by the non-everted gut sac method. The optimized NRG-LNCs had a hydrodynamic diameter of 29.41±1.25 nm, a low polydispersity index, and high entrapment efficiency of 99.25±2.31%. The LNCs could retain NRG radical scavenging activity, showed good storage stability, and significantly improved NRG solubility (69 fold) and permeation through non-everted rat intestinal sac (4.33 fold). LNCs of NGR enhance solubility and intestinal permeability of this flavonoid and may be useful in the improvement of its bioavailability.

Role of interleukin 1 beta in the regulation of rat intestinal multidrug resistance-associated protein 2 under conditions of experimental endotoxemia

Multidrug resistance-associated protein 2 (Mrp2), expressed at the brush border membrane (BBM) of the enterocyte, is an ABC transporter with relevant intestinal barrier function. Its toxicological relevance lies in preventing absorption and tissue accumulation of dietary contaminants, drugs, and potentially harmful endogenous metabolites. Expression and activity of intestinal Mrp2 is downregulated in LPS-induced endotoxemia. In addition, confocal microscopy studies demonstrated internalization of the transporter to endocytic vesicles. Since IL-1β plays an important role as early mediator of LPS-inflammatory responses, we evaluated whether IL-1β mediates LPS-induced impairment of Mrp2 function. Two protocols were used: I) In vivo administration of LPS (5 mg/kg b.wt., i.p., single dose) to rats in simultaneous with administration of anti-IL-1β (25 μg/kg b.wt., i.p., 4 doses), followed by studies of Mrp2 expression, localization and activity, 24 h after LPS administration; II) In vitro incubation of isolated intestinal sacs with IL-1β (10 ng/mL) for 30 min, followed by analysis of Mrp2 activity and localization. We found that in vivo immunoneutralization of IL-1β partially prevented the decrease of Mrp2 protein expression and activity as well as its internalization to intracellular domains induced by LPS. Involvement of IL-1β in the alteration of Mrp2 localization and activity was more directly demonstrated in isolated intestinal sacs, as incubation with IL-1β resulted in detection of Mrp2 in intracellular regions of the enterocyte in simultaneous with alteration of transport activity. In conclusion, IL-1β induces early internalization of intestinal Mrp2, which could partially explain loss of expression at the BBM under conditions of experimental endotoxemia. Concomitant impairment of Mrp2-dependent barrier function may have pathophysiological relevance since IL-1β mediates the effect of many local and systemic inflammatory processes.

Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes

Background: The study was aimed to prepare and evaluate tamoxifen loaded controlled release liposomes to reduce the side effects of tamoxifen during cancer treatment. &#x0D; Methods: Different tamoxifen loaded liposomes were prepared by modified ether injection (MEIM) and thin film hydration method (TFHM) under prescribed conditions. The prepared liposomes were characterized by using optical microscopy, evaluating encapsulation efficiency, in-vitro and ex-vivo diffusion studies by using dialysis membrane and chicken intestinal sac respectively.&#x0D; Results: The data revealed that all of the liposomes were spherical in shape and stable under three physical conditions i.e. 4, 25 and 37 ± 2°C temperatures and 60 ±5% relative humidity. Additionally most of the liposomes followed zero order and class II release kinetics. It was also observed that with the increase of phospholipids and cholesterol, entrapment efficiency of liposome vesicles increased thus giving a controlled release drug delivery system but further increase reduced this efficiency at a certain level.&#x0D; Conclusion: The formulated control release liposomes might be a good drug delivery system for target oriented drug delivery with minimum side effects of tamoxifen during cancer treatment.

Bioactive Peptide Tempe Made from Mucuna pruriens (L) DC as an Inhibitor of Angiotensin-I-Converting Enzyme (ACE) in a Digestion Simulation.

Mucuna pruriens (L) DC tempe is a food that functions as an inhibitor of the angiotensin-I-converting enzyme (ACE). The purpose of this research was to study the activity of M. pruriens tempe peptides during the digestive process in vitro with pepsin-pancreatin, and absorption of peptides in the small intestine using the inverted intestinal sac method. Our results show that M. pruriens had the highest ACE-inhibiting activity after digestion in vitro after fermentation for 72 h (F72). F72 peptide absorption (%) and ACE-inhibitory activity of the absorbed peptides did not significantly differ between the different segments of the small intestine (duodenum, jejunum, and ileum). These results demonstrate that F72 tempe maintains ACE-inhibitory activity in each segment of the small intestine after both digestion and absorption.

Molecular pharmacokinetic mechanism of the drug-drug interaction between genistein and repaglinide mediated by P-gp

This study was devised to investigate if P-glycoprotein (P-gp) mediated the drug–drug interaction (DDI) between genistein and repaglinide. When genistein was added, the plasma concentrations of repaglinide in rats were increased. The maximum plasma concentration (Cmax) of repaglinide increased from 70.80 ± 7.98 ng/mL to 124.71 ± 9.02 ng/mL and the area under the plasma concentration-time curve (AUC) increased from 134.89 ± 13.65 μg·h/L to 245.95 ± 7.24 μg·h/L. Intestinal absorption of repaglinide was markedly enhanced by genistein or P-gp inhibitor verapamil (Ver), both in situ rat jejunal perfusion studies and in vitro transport assays using everted rat intestinal sac preparations. Furthermore, the accumulation of repaglinide in both Caco-2 cells and IEC-6 cells also increased significantly in the presence of genistein and Ver. The transepithelial transport rate of repaglinide from basolateral-to-apical in MDR1-MDCK cells was 3.6-fold higher than the apical-to-basolateral rate with a net efflux ratio of 1.92 compared with mock-MDCK cells, which was significantly decreased following co-administration with genistein or Ver. In an intracellular accumulation experiment using Rhodamine 123 as a P-gp substrate, genistein significantly increased the intracellular fluorescence of Rhodamine 123. These results indicated that genistein had an inhibitory effect on the efflux function of P-gp. Through molecular docking assays we further found that genistein could bind to the nucleotide-binding domains (NBD) in the cytoplasm of P-gp, thus affecting the functions of P-gp. In conclusion, genistein inhibited the efflux of repaglinide mediated by P-gp in rats and in vitro. The findings suggested that the DDI between genistein and repaglinide is mediated by P-gp, and a dosage adjustment may be needed when they are co-administered in a clinical setting.

Bioavailability and prebiotic potential of Carapax Trionycis, a waste from soft‐shelled turtle processing

Carapax Trionycis is the shell of the soft-shelled turtle. It is rich in minerals, amino acid, peptides, and other nutrients. Current processing and consumption of soft-shelled turtle leads to the waste of huge quantities of Carapax Trionycis in the form of spent materials. In this study, the bioavailability, prebiotic activity, and physicochemical properties of Carapax Trionycis using different processing methods were investigated. The vinegar-quenched Carapax Trionycis (V-CT), fine powders (D0.18, D0.10), and superfine powders (D0.05, D0.025) of Carapax Trionycis were prepared by the vinegar-quenching method, common grinding, and the superfine grinding method. The average particle sizes of D0.18, D0.10, D0.05, and D0.025 were 147.82, 77.35, 36.65, and 2.24 μm, respectively. Superfine grinding changed the surface morphology of Carapax Trionycis and promoted the release of active ingredients. D0.025 had the highest polypeptide (8.15%), polysaccharide (1.21%), total free amino acid (232.36 mg 100 g-1 ) and water-soluble extract content (10.74%), and showed the highest calcium release rate (55.64%) after in vitro digestion. The apparent permeability (PAPP ) of the resulting Carapax Trionycis samples in the dialysis tubing model and the everted intestinal sac model increased significantly with the decrease in the Carapax Trionycis particle sizes. Furthermore, the five Carapax Trionycis samples significantly stimulated the growth of the tested probiotics and increased lactic acids production after 48 h fermentation compared to the control. The Carapax Trionycis powder prepared by superfine grinding displayed better prebiotic activity than other samples as it significantly induced a greater proliferation of probiotic bacteria and higher production of lactic acid, as well as greater release of free calcium. The results showed that Carapax Trionycis superfine powder D0.025 had the highest active ingredient content, calcium bioavailability, and prebiotic activity. Our approach of developing Carapax Trionycis superfine powder as natural calcium supplement or potential prebiotic would therefore broaden the scope of soft-shelled turtle processing waste utilization in an eco-friendly, cost-effective, and sustainable approach in the future. © 2020 Society of Chemical Industry.

Development of Lipid-Based Nanocarriers for Increasing Gastrointestinal Absorption of Lupinifolin

Lupinifolin, a plant flavonoid, has been reported to possess various pharmacological effects. It most likely exerts low oral bioavailability because of poor water solubility. The objective of this study was to develop lipid nanocarriers as drug delivery systems to increase the gastrointestinal absorption of lupinifolin extracted from Albizia myriophylla. Three types of nanocarriers, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were prepared by an emulsification-sonication technique. All three types of nanocarriers loaded with lupinifolin, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were successfully synthesized. The lipid components chosen to formulate nanocarriers were tripalmitin and/or medium chain triglyceride. Physicochemical characterizations along with releasing profiles of lupinifolin-loaded lipid nanocarriers were compared. It was found that the best lipid nanocarrier for lupinifolin was lupinifolin-loaded nanostructured lipid carriers, which demonstrated the particle size of 151.5 ± 0.1 nm, monodispersity distribution with a polydispersity index of 0.24, negative surface charge at - 41.2 ± 0.7 mV, high encapsulation (99.3%), and high loading capacity (5.0%). The obtained lupinifolin-loaded nanostructured lipid carriers exhibited prolonged release in a simulated circulatory system but produced a low release in gastrointestinal conditions (3.7%). Intestinal permeability of the nanocarriers was further evaluated in everted intestinal sacs. The results from the ex vivo study indicated that lupinifolin-loaded nanostructured lipid carriers significantly increased the absorption of lupinifolin compared to the native form. In conclusion, lupinifolin-loaded lipid nanocarriers were successfully formulated as delivery systems to enhance its oral bioavailability. Further in vivo experiments are needed to validate the results from this study.

Kaempferia parviflora Nanosuspension Formulation for Scalability and Improvement of Dissolution Profiles and Intestinal Absorption.

Kaempferia parviflora (KP) is an herbal medicine for enhancement of physical fitness and male sexual function improvement with low oral absorption of the main active compounds, methoxyflavones. The purpose of this study is to optimize the preparation of nanosuspensions of KP extract for enhancing intestinal absorption using antisolvent precipitation technique which is an accessible nanomanufacturing methodology in the small industrial factory. Nanosuspensions were prepared using various types and concentrations of stabilizers. Then, the dry powder of KP nanosuspension was produced by spray drying. Its dissolution rate was determined using USP dissolution apparatus II. The rat everted intestinal sac was tested to confirm the improvement of intestinal absorption of KP nanosuspension. The result showed that 3% sodium lauryl sulfate (SLS) was the optimal condition for covering the nano-size of KP nanosuspension. KP nanosuspensions had particle sizes ranging from 100 to 300 nm with narrow size distribution (PDI < 0.60) and zeta potential at - 58 to - 70 mV. These characteristics were stable at 4°C and 25°C/60%RH for 1-month storage. Its methoxyflavones content also unchanged at 4°C and 25°C/60%RH for 1-month storage. KP nanosuspension released > 80% of the methoxyflavones within 30 min both in 0.1 N HCl and 0.01 M phosphate buffer solution (pH 6.8). Moreover, the developed nanosuspension dramatically improved the rat intestinal absorption about 10-fold. Therefore, the KP nanosuspension was successfully prepared. It has relatively high stability, fast dissolution rate, and high intestinal absorption.

Isolation and molecular identification of wild Newcastle disease virus isolated from broiler farms of Diyala Province, Iraq

Background and Aim:Newcastle disease virus (NDV) remains a major viral disease of poultry. The morbidity and mortality rates of chickens vaccinated with NDV in broiler farms in Diyala Province were 100% and 80%, respectively, rates due to suspected infection with the highly virulent NDV. The present study aimed to isolate and identify the NDV virus and evaluate its pathogenicity in infected broiler chickens at poultry farms.Materials and Methods:Broiler chickens at two commercial poultry farms were suspected of being infected with virulent NDV due to high mortality rates. Virus isolated from samples of intestinal tissues, lungs, trachea, spleen, kidneys, and air sacs was adapted in the allantoic cavity of embryonated specific-pathogen-free (SPF) chicken eggs. The NDV pathotype was determined based on the mean death time (MDT) in eggs as well as the intracerebral pathogenicity index (ICPI) and intravenous pathogenicity index pathogenicity indexes of the isolated samples. Broilers were experimentally infected by inoculation with fluids collected from the allantoic cavities of 60 broilers aged 35 days. Serological and molecular tests were followed by enzyme-linked immunosorbent assay to determine levels of anti-NDV immunoglobulin G, and isolates were identified using a hyperimmune (HI) test and real-time polymerase chain reaction (RT-PCR).Results:Suspected and isolated NDV field samples propagated in the allantoic cavity of 10-day-old fertile SPF chickens were NDV positive in the rapid hemagglutination test within a few seconds. Pathogenicity indices and MDT showed that the isolated NDV was viscerotropic and velogenic. The virus was identified as NDV by the HI test using specific anti-LaSota HI serum and RT-PCR with specific primers and probes. Propagation of the virus in the allantoic cavity of embryonated hen eggs produced a viral titer of 109.5 EID50/0.1 mL.Conclusion:The virus isolated from broiler chicken farms in Diyala Province, Iraq, was viscerotropic and velogenic according to the pathogenicity indices and RT-PCR. The isolated NDV caused 100% morbidity and 90% mortality in NDV-vaccinated and experimentally infected broiler chickens.

Analysis of five active ingredients of Er-Zhi-Wan, a traditional Chinese medicine water-honeyed pill, using the biopharmaceutics classification system.

Er-Zhi-Wan (EZW) is a traditional Chinese medicine with many clinical applications and used as a health product in East Asia. Five active ingredients (salidroside, specnuezhenide, nuezhenoside, luteolin, and oleanolic acid) were screened out from EZW to develop an in vitro rapid evaluation method for the classification of in vivo drug absorption behavior by biopharmaceutics classification system (BCS). Ultra-performance liquid chromatography was used for quantitative analysis. Solubility and permeability were assayed by equilibrium solubility and multiple models: everted rat intestinal sac model, cultured Caco-2 cells, octanol-water partition coefficient (LogP) method. The BCS properties of drugs were predicted using software applications, and the correlations of measured and predicted values of factors affecting oral drug absorption were calculated. The results were verified by measuring the absolute bioavailability of the active ingredients. Salidroside, specnuezhenide, and nuezhenoside were classified as BCS class III drugs, and luteolin was classified as a BCS class III/I drug because of the difference in LogP and intestinal permeability. Oleanolic acid was classified as a BCS class II/IV drug in acidic media and BCS class I/III drug in other media. Overall, EZW may be classified as a BCS class III drug, and permeability was identified as the primary factor limiting absorption. The results provide a novel method for the evaluation of the in vivo absorption of oral traditional Chinese medicines.

Particle engineering of fenofibrate for advanced drug delivery system

BackgroundThe goal of the current investigation was to formulate, evaluate co-crystal, and further design of solid unit dosage form of antihyperlipidemic BCS class II drug fenofibrate (FNO). Co-crystals composed of a structurally homogeneous crystalline material that contains two or more components in a definite stoichiometric amount helps in increasing yield, the capability to regulator polymorph fabrication, enhanced invention crystallinity. Ball milling method is used for co-crystal formulation, optimized via 32 full factorial design and characterized by saturation solubility, particle size analysis, Fourier transform infrared spectroscopy (FT-IR) study analysis, powder X-ray diffraction (PXRD) study analysis, surface morphology by scanning electron microscopy (SEM) study, flow properties, and ex vivo intestinal permeation study via non-everted rat intestinal sac model. Furthermore, optimized batch compressed into tablets is evaluated for disintegration time, hardness, friability, in vitro drug release study and stability study.ResultsIt demonstrated that co-crystal formulation FNOCC7 shows higher saturation solubility 0.3874 ± 2.82 g/ml with less particle size 221.231 ± 0.456 nm, FT-IR spectra confirmed significant structural alterations in the formulation indicating the hetero-molecular interaction, the presence of hydrogen bonding had occurred in the co-crystals, PXRD spectra of formulation determined by the increase in the crystalline nature. FNO co-crystals show flux (F) and permeability coefficient (Papp) 0.322 ± 0.068 μg/min, 5.38 ± 0.093 cm/min respectively increased compared to the pure drug makes in an enhancement of solubility as well as the bioavailability of BCS class II drug.ConclusionsThe solubility and dissolution percentage of FNO can be improved by the utilization of Co-crystal of FNO with PEG 4000. The solubilization impact of PEG 4000 might be contributed because of the decrease of molecule conglomeration of the drug presence of crystallinity, expanded wettability, and dispersibility; pharmaceutical co-crystals speak to a beneficial class of crystal form with regard of pharmaceuticals.

P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies

In vitro studies showed that 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) increases P-glycoprotein (P-gp) expression and activity in Caco-2 cells, preventing xenobiotic toxicity. The present study aimed at investigating TX5 effects on P-gp expression/activity using Wistar Han rats: a) in vivo, evaluating intestinal P-gp activity; b) ex vivo, evaluating P-gp expression in ileum brush border membranes (BBM) and P-gp activity in everted intestinal sacs; c) ex vivo, evaluating P-gp activity in everted intestinal sacs of the distal and proximal ileum. TX5 (30 mg/kg, b.w.), gavage, activated P-gp in vivo, given the significant decrease in the AUC of digoxin (0.25 mg/kg, b.w.). The efflux of rhodamine 123 (300 μM), a P-gp fluorescent substrate, significantly increased in TX5-treated everted sacs from the distal portion of the rat ileum, when P-gp activity was evaluated in the presence of TX5 (20 μM), an effect abolished by the P-gp inhibitor verapamil (100 μM). No increases on P-gp expression or activity were found in TX5-treated BBM of the distal ileum and everted distal sacs, respectively, 24 h after TX5 (10 mg/kg, b.w.) administration. In vivo, no differences were found on digoxin portal concentration between control (digoxin 0.025 mg/kg, b.w., intraduodenal) and TX5-treated (digoxin+TX5 20 μM, intraduodenal) rats. The observed discrepancies in digoxin results can be related to differences in TX5 dose administered and used methodologies. Thus, the results show that TX5 activates P-gp at the distal portion of the rat ileum, and, at the higher dose tested (30 mg/kg, b.w.), seems to modulate in vivo the AUC of P-gp substrates.

Antihyperglycemic potential of Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle for in vitro intestinal glucose absorption in diabetic albino rats

Objective: To evaluate the antihyperglycemic potential of the Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion for in vitro intestinal glucose absorption in Rattus norvegicus of the Holtzman strain with chemically-induced diabetes. Materials and methods: The study had an experimental and analytical design. A phytochemical screening of the whole plant was carried out. For the in vitro study, twenty male albino rats were induced with diabetes using alloxan monohydrate (Sigma-Aldrich, Saint Louis, MO, USA) at a dose of 120 mg/kg bw administered by intraperitoneal route, and then randomly distributed into two groups of ten albino rats each. After ten days, they were sacrificed to extract an intestinal segment using the everted intestinal sac technique, and measure the glucose transport and absorption. In the control group (everted intestines incubated in Krebs-Henseleit solution containing glucose) and the experimental group (intestines incubated in Krebs-Henseleit solution containing glucose plus the Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion at 10% w/v), basal samples of fluids were taken from incubation, and then other samples were taken at 15, 30, 45 and 60 minutes to quantify the glucose from the mucous and serous compartments using the glucose oxidase enzymatic method.Results: Lower concentrations of absorbed glucose were observed in the intestinal serous compartment of the experimental group (G. gilgiana) with a statistically significant difference compared to the control group (p <0.05). Conclusions: The Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion exhibits a significant antihyperglycemic potential by decreasing the in vitro intestinal glucose absorption in diabetic albino rats.

Permeability of Piroxicam with Sodium Lauryl Sulfate as Surfactant

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) which have characteristic insoluble in water and poorly fluidity. The profile absorption from piroxicam was depend on its dissolution rate in the gastrointestinal tract (GI). To improve the solubility in the water, it can used Sodium Lauryl Sulfate (SLS) as a surfactant which have mechanism by forming a micelle. The aim of this study was to measure the influence gradiet concentration of SLS with Piroxicam absorption that can observe by inverted intestinal sac method. The concentration of piroxicam solution that added by SLS are 1, 2, and 3% respectively. The preparation method using Crane and Wilson tube containing mucosal fluid. After preparation, it was taken at 37°C in waterbath and added with serosal solution to intestinal sac by turned upside down and tied to a cannula. The sample was placed in the tube containing mucosal fluid and constantly flowing by oxygen gas. To measure the absorsion of piroxicam that used serosal solution which every 15 minutes was taken on tube. After this, it was diluted using Ba(OH)2 and ZnSO4 then continuous with separating process. The absorbant of supernatant was measured using Spectrophotometer UV-Vis. Data analyse was calculated by one-way ANOVA. According to Pm, the values 0.25x10-3 cm/minute (0% SLS), 0.39x10-3 cm/minute (1% SLS), 1.45x10-3 cm/minute (2% SLS) and 1.26x10-3 cm/minute (3% SLS) respectively. In conclusion, 2 % SLS significantly give the highest absorption of piroxicam by altering the membrane permeability.