Intestinal Media Research Articles

Intestinal microbiota composition in broilers fed protein-free or casein-based diets

Growing broiler chickens of the Cobb500 strain were used to determine the effects on intestinal microbiota composition of a protein-free (PF) diet as compared to a diet based in casein (CAS) as the only protein source. CAS was formulated to contain the same amount of protein (190 g kg-1) as a commercial Maize-soy diet which was used as a practical reference. The ileal AA flow (g kg-1 dry matter intake) was significantly higher (P < 0.001) than PF in birds fed protein containing diets (CAS or Maize-soy). Taken as a whole (discriminant and ANOSIM analysis), the intestinal (ileal and caecal contents and ileal tissue) microbiota composition of PF and CAS were significantly (P < 0.001) different from Maize-soy and not different from each other in some cases. RT-qPCR and sequencing analysis of the ileal and caecal microbiota revealed significant (P < 0.05) differences in a number of bacterial groups between broilers fed PF, CAS or Maize-soy diets. The main result was that the lack of protein in the intestinal medium of PF birds resulted in a drop of Lactobacillus spp. counts (on average, 43 in PF vs 1,734 in the Maize-soy diet) and increased Enterobacteriaceae (on average, 419 in PF vs 172 in the Maize-soy diet) and other potentially pathogenic bacterial groups (in both intestinal contents and tissue). Thus, the lack of protein in the intestinal medium of PF birds resulted in a microbiota composition compatible with a pro-inflammatory state, and this effect was somewhat less marked in birds fed CAS. The results reported here suggest that the adverse effects on microbiota composition in broilers fed CAS were less marked than in those fed PF, which would be in line with a preferential use of a highly digestible protein containing diet to determine endogenous AA excretion instead of a PF diet.

Comparative Evaluation of Micellization and Cellular Uptake of β-Carotene Affected by Flavonoids.

Based on in vitro digestion, micellar synthesis, and Caco-2 cell model, this study investigated the effects of typical flavonoids in citrus (naringenin, naringin, hesperetin, hesperidin, quercetin, and rutin) at different doses on the micellization and cellular uptake of β-carotene. In in vitro digestion, low-dose flavonoids enhanced β-carotene bioaccesssibility by regulating the stability and dispersibility of the intestinal medium, particularly quercetin, which significantly increased the bioaccessibility by 44.6% (p < 0.05). Furthermore, naringenin, hesperetin, hesperidin, and quercetin enhanced the micellar incorporation rate of β-carotene; however, naringin and rutin exhibited an opposite effect, particularly naringin, which significantly reduced it by 71.3% (p < 0.05). This phenomenon could be attributed to the high solubility of naringin and rutin in micelles, resulting in a competitive inhibitory effect on β-carotene. Besides, all treatments significantly enhanced β-carotene cellular uptake (p < 0.05) by promoting the expression of scavenger receptor class B type I and Niemann-Pick C1-Like 1.

EFFICIENT DRUG CARRIER FOR ACETYLSALICYLIC ACID FROM CHITOSAN-BASED COMPOSITES PREPARED WITH MONTMORILLONITE, CELLULOSE, AND HYDROXYAPATITE

In this study, chitosan-based hydroxyapatite/chitosan (HAP/CHI), cellulose/chitosan (CEL/CHI) and montmorillonite/chitosan (MMT/CHI) composites were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Thermogravimetric Analysis (TGA). Acetylsalicylic acid (ASA) was used as a drug for loading and desorption studies to determine the release behavior of the synthesized composites. The maximum adsorption capacities (qe) were obtained as 251.5 mg/g, 197.7 mg/g and 288.95 mg/g for HAP/CHI, CEL/CHI and MMT/CHI, respectively. In vitro release studies of ASA from the composites HAP/CHI, CEL/CHI, and MMT/CHI were carried out phosphate buffer solution (PBS) and gastric juice (GJ). In the intestinal medium (PBS) controlled drug release continued for 72 hours (4320 minutes), and burst release was observed in the first 5 minutes in all composites. 19.16%, 47.15% and 37.32% of the active ingredient from HAP/CHI, CEL/CHI and MMT/CHI composites, respectively, were released in the first 5 minutes. After 5 minutes, the release slowed down and became more controlled for all three composites. At the end of the release, the highest releasing composite was CEL/CHI, with 95.77% ASA release. A total drug release of 87.48% was achieved with MMT/CHI and 87.37% with HAP/CHI. In the gastric environment (GJ) Controlled drug release continued for 72 hours (4320 minutes), and burst release was observed in the first 5 minutes in all composites. 52.51%, 72.30% and 44.87% of the active ingredient from HAP/CHI, CEL/CHI and MMT/CHI composites, respectively, were released in the first 5 minutes. After 5 minutes, the release slowed down and became more controlled for all three composites. At the end of the release, the highest releasing capacity was found with the CEL/CHI composite, with 96.05% ASA release. A total drug release of 93.26% was achieved with HAP/CHI and 84.89% with MMT/CHI.

Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.Graphical

Effects of film-forming components on the viability of probiotics and the application of synbiotic pectin film in preserving Da Xanh pomelo and Thai jackfruit fresh-cut.

Minimally processed products are highly convenient, and fresh-cut fruits coated with the synbiotic film have many advantages. This study investigated the film-forming components and preservation ability of Da Xanh pomelo and Thai jackfruit fresh-cut by synbiotic pectin film. The results showed that PA70 film combined with 1.5% FOS (fructooligosaccharides) had the highest number of viable cells of L. plantarum after 30days of storage at 5°C. The number of probiotic cells existing on fresh-cut products of Da Xanh pomelo and Thai jackfruit was always high (> 8 log CFU/g) and stable during 10days of storage. In addition, jackfruit and pomelo fresh-cut preserved with probiotic film also showed probiotic activity in simulated stomach and small intestine medium with the number of probiotic cells (> 6 log CFU/g) and survival cell ratio after 4h in small intestine medium reached 81.20 ± 0.92% (pomelo) and 82.16 ± 0.94% (Thai jackfruit).

Towards a novel pullulan and pullulan-enteric hard capsules: Study of drug release and crucial capsule features

Pullulan, a natural polymer, is often used as a plant-based alternative polymer for gelatin to produce hard capsules. To the best of our knowledge, there have been negligible studies on the performance of enteric pullulan capsules. Hence, this paper describes a new formulation for enteric pullulan hard capsules that can resist the acidic environment of the stomach and release the drug in the small intestine without the need for an exterior coating. This formulation consists of three polymers, including pullulan, Eudragit L100, and κ-carrageenan, which are used to develop resistance against acid and facilitate gelation to form capsules. With regards to the humidity assessment of target hard capsules, it is estimated that the prepared capsules possess an appropriate potential for target utilizations. The capsules were tested using esomeprazole as a model drug for dissolution testing. The results demonstrated that the enteric hard-shell capsules remained stable for 2 h in 0.1 N HCl at a pH of 1.2 and then ruptured upon entering a phosphate buffer (simulated small intestine) medium at a pH of 6.8. The FESEM and cross-sectional analysis revealed that no drug was released due to the absence of pores on the surface. Rheological examinations also revealed that the prepared solution have a desirable property. It is certified that the NMR spectrum proposes the existence of crosslinking and polymerization of pullulan which signifies appropriate existing interactions polymeric binders and gelling agent. TGA and DSC evaluations are in well accordance with the strong cross-linked structure generated by comprising pullulan polymer with the Eudragit pH-sensitive Polymer. Overall. this new formulation has potential feature for utilization in drug delivery systems where controlled release is desired, especially for drugs that are sensitive to acidic environments in the stomach.

Novel formulation of uncoated enteric capsule shells: Study the effect of gelling agents and salts on the rheology and physical properties

Currently, pharmaceutical technology offers new choices for protecting acid-sensitive substances from the stomach environment by dosage form of an enteric coating or the encapsulation of drugs in enteric capsules. Coating gelatin capsules is challenging, cost-intensive, and energy-consuming, as the smoothness of their surface hinders the adhesion of the film. In this study, the formulation of an uncoated gelatin-based enteric capsule shell composite is developed. The effect of four different gelling agents and six salts on the preparation of capsules is investigated. Potassium acetate (KAC) and κ-carrageenan are examined and selected as the best salt and gelling agent, respectively. The physicochemical, surface, and cross-section morphology, mechanical, and drug release properties of prepared enteric capsules (without (F1) and with (F2) gelatin) were characterized. The drug release of optimized capsules (F1, F2) was tested using pantoprazole. The results showed high stability (120 min) of prepared capsules in the stomach environment with no release (pH = 1.2), and then started to release in the intestinal medium (pH = 6.8) after 16 min, which is great according to the definition of the enteric capsule. Furthermore, the tensile strength of gelatin-based enteric capsules and pure gelatin capsules was tested and compared.

PHYSICOCHEMICAL AND BIOSPECIFIC PROPERTIES OF A POROUS CARBON SORBENT MODIFIED WITH SULPHOSALICYLIC ACID

A mesoporous carbon sorbent modified with sulphosalicylic acid by adsorption from aqueous solutions has been synthesized. The optimal modification parameters were selected: the ratio, concentration, the duration of impregnation and heat treatment stages, and pH. The physicochemical properties of the samples have been studied: textural characteristics, qualitative and quantitative composition of surface functional groups, the amount of applied modifier, adsorption and desorption properties. The adsorption characteristics of the studied samples with respect to organic dyes methylene blue and methanyl yellow are determined. It has been established that during desorption for 48 h, ~ 68% and ~ 82% of the initial concentration of sulphosalicylic acid applied to the sample pass into the aqueous solution, modelling the intestinal medium and into ethanol, respectively. In this case, a decrease in the pH of the initial solutions by 6 units is observed. High antibacterial properties of the modified carbon sorbent towards Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae have been established in vitro.

Development of Chitosan/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer/Polymer and Drug/Polymer Interactions' Effects on Kinetic Models.

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer-Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.

Development, optimization and in vitro-in vivo evaluation of solid lipid microparticles for improved pharmacokinetic profile of bisoprolol

The current research aimed at designing and optimizing controlled release solid lipid microparticles (SLMs) of Bisoprolol (BPL) from biocompatible waxes by using Box-Bhenken design (BBD) for improving the drug pharmacokinetics, enhancing compliance in hypertensive patients as well as eliminating inefficiencies of traditional methods of drug delivery. Seventeen formulations (F1 to F17) of controlled release BPL loaded SLMs were made by melt emulsification technique where Carnauba wax (CW) and Ceresin wax (CSW) were used as carriers and Tween 80 was used as stabilizer. The SLMs were characterized using fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Results revealed that micromeritics properties of all SLMs were satisfactory and showed good percentage yield (PY) and entrapment efficiency (EE). The minimum EE was observed by formulation-1 (F1) as 21.66% whereas F3 has showed maximum EE as 88%. Results of in vitro release study revealed that all formulations showed a well-controlled release in simulated intestinal medium at pH 7.4. The formulation F3 with high wax concentration revealed best extended release characteristics (29%) in 12 h. The pharmacokinetics studies of SLMs demonstrated an expressively lower Cmax (maximum plasma concentration) of BPL (53.61 ± 2:52) with a satisfactorily higher time to achieve maximum plasma concentration (Tmax) of 10.24 h as compared to Cmax (79.63 ± 5.75) and Tmax (2.45 ± 3.83) of BPL released from commercial brands. Moreover the attainment of greater bioavailability of BPL was most probably due to the increase in half-life (20.44 ± 2.82), mean residence time (24.81 ± 4.22) and area under the plasma concentration level curve (AUC0–24) of 9688.6 ± 4.18 for BPL released from SLMs. Convincingly, the inventive technique could not only sustain the drug release in the in vitro and in vivo environment but also maintain the plasma drug concentration level constant for a longer time without elevating Cmax.

Functional properties and bioaccessibility of alginate based phycocyanin-honey hydrogels

Food gels have become attractive due to their biocompatibility, environment-friendly characteristics, and wide array of medical and food applications. One of the main design principles of a functional food matrix is the encapsulation, protection, and controlled release of nutraceuticals. The present study utilized two products having great interest recently, phycocyanin and honey, which were embedded in a gel-type delivery system composed of different concentrations of alginate (0.5, 1.0, 1.5, and 2.0 g/100 mL) and gelatin (7 g/100 mL). The phycocyanin-honey gel balls (PHB) were characterized in terms of physical, rheological, textural, morphological, and sensory properties, as well as in vitro digestion, bio-accessibility, and total phenolic content release kinetics. The increasing alginate concentration significantly increased (p<0.05) total phenolic content. Also, increasing alginate ratios caused sheet-like inner layers observed in scanning electron microscopy (SEM) images. In vitro digestibility of phenolic content derived from both honey and phycocyanin was significantly improved (p<0.05) and protected from the mouth and gastric medium by hydrogel structures of alginate and gelatin. PHB showed high release (>≈85 %) and bio-accessibility (>≈84 %) of phenolic content in the intestinal medium. Consequently, alginate could be successfully used at 1.5 g/100 mL concentration with gelatin to enhance the functionality and bio-accessibility of functional ingredients without affecting sensory properties.

Optimization of extraction and nanoencapsulation of kimchi cabbage by-products to enhance the simulated in vitro digestion of glucosinolates

Kimchi cabbage is a well-known glucosinolate (GLS)-containing vegetable, but its by-products are discarded despite the presence of GLS. The aim of this study was the optimization of the extraction and nanoencapsulation of GLS from kimchi cabbage by-products to enhance the intestinal absorption of GLS. The optimal GLS extraction conditions included steaming thrice as pretreatment, utilizing 70% methanol, and ultrasonication at 20% amplitude for 15 min. Under these conditions, 80.11 ± 4.40 mg/100 g of GLS extraction was obtained and the extraction yield was 81.70 ± 4.73%. The optimized kimchi cabbage by-product extract (KCE) was coated with chitosan-lipid nanoparticles (KCE-NPs) and their stability and release under simulated in vitro gastrointestinal conditions were evaluated. KCE-NPs protected the encapsulated GLS under acidic gastric conditions and released 91.63 ± 0.76% of GLS in the simulated intestinal medium. Therefore, the proposed KCE-NPs are a promising delivery system for increasing GLS absorption.

Lyophilized nano-liposomal system for red onion (Allium cepa L.) peel anthocyanin: Characterization, bioaccessibility and release kinetics

In recent years, there has been extensive research on valorization of food wastes and a growing interest in nano-liposomal systems for food applications. This paper discusses the case of phosphatidylcholine basednanophytosomes loaded with anthocyanins extracted from red onion (RNPs) to overcome the bio-stability during digestion. The characterization of lyophilized RNPs in terms of entrapment efficiency, particle size, poly-dispersity index (PDI), ζ-potential, morphological properties, in vitro bioaccessibility and release kinetics were investigated. Entrapment efficiency was determined as 78.63% with lowest particle size (177.73 nm) and PDI value (0.45) and non-dense spherical microstructure for RNP6 (red onion peel anthocyanin extract: soybean phosphatidylcholine at 1:6 ratio). Apart from the particle size, entrapment efficiency was determined higher than 75%, which indicates good entrapment. Additionally, from the cumulative release of RNPs concluded as a successful nano-structure with a two-fold increase in intestinal medium. However, poor Carr index and Hausner ratio suggest some limitations of the current nanoliposomes process which could be further improved. Red onion peel wastes, which are typically discarded, can serve as excellent sources of anthocyanins, and its preparation to nanophytosomes could be used as functional food ingredient or food supplements.

A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

Newly Synthesized Lignin Microparticles as Bioinspired Oral Drug-Delivery Vehicles: Flavonoid-Carrier Potential and In Vitro Radical-Scavenging Activity.

The aim of the present study was to synthesize lignin microparticles, to evaluate their physicochemical, spectral, morphological and structural characteristics, to examine their encapsulation and in vitro release potential and behaviour towards the flavonoid morin in simulated physiological medium and to assess the in vitro radical-scavenging potential of the morin-loaded lignin microcarrier systems. The physicochemical, structural and morphological characteristics of alkali lignin, lignin particles (LP) and morin-encapsulated lignin microparticles (LMP) were determined based on particle size distribution, SEM, UV/Vis spectrophotometric, FTIR and potentiometric titration analyses. The encapsulation efficiency of LMP was 98.1%. The FTIR analyses proved that morin was successfully encapsulated in the LP without unexpected chemical reactions between the flavonoid and the heteropolymer. The in vitro release performance of the microcarrier system was successfully mathematically described by Korsmeyer-Peppas and the sigmoidal models outlining the general role of diffusion during the initial stages of the in vitro release process in simulated gastric fluid (SGF), and the predominant contribution of biopolymer relaxation and erosion was determined in simulated intestinal medium (SIF). The higher radical-scavenging potential of LMP, as compared to that of LP, was proven via DPPH and ABTS assays. The synthesis of lignin microcarriers not only provides a facile approach for the utilization of the heteropolymer but also determines its potential for the design of drug-delivery matrices.

Chitosan/Albumin Coating Factorial Optimization of Alginate/Dextran Sulfate Cores for Oral Delivery of Insulin.

The design of nanoparticle formulations composed of biopolymers, that govern the physicochemical properties of orally delivered insulin, relies on improving insulin stability and absorption through the intestinal mucosa while protecting it from harsh conditions in the gastrointestinal (GI) tract. Chitosan/polyethylene glycol (PEG) and albumin coating of alginate/dextran sulfate hydrogel cores are presented as a multilayer complex protecting insulin within the nanoparticle. This study aims to optimize a nanoparticle formulation by assessing the relationship between design parameters and experimental data using response surface methodology through a 3-factor 3-level optimization Box-Behnken design. While the selected independent variables were the concentrations of PEG, chitosan and albumin, the dependent variables were particle size, polydispersity index (PDI), zeta potential, and insulin release. Experimental results showed a nanoparticle size ranging from 313 to 585 nm, with PDI from 0.17 to 0.39 and zeta potential ranging from -29 to -44 mV. Insulin bioactivity was maintained in simulated GI media with over 45% cumulative release after 180 min in a simulated intestinal medium. Based on the experimental responses and according to the criteria of desirability on the experimental region's constraints, solutions of 0.03% PEG, 0.047% chitosan and 1.20% albumin provide an optimum nanoparticle formulation for insulin oral delivery.

Formulation and Evaluation of Xanthan Gum Microspheres for the Sustained Release of Metformin Hydrochloride.

This work aimed to formulate xanthan gum microspheres for the encapsulation of metformin hydrochloride, according to the process of ionotropic gelation. The obtained microparticles, based on various fractions of xanthan gum (0.5-1.25), were subjected to different physico-chemical tests and a drug release study. Microspheres with an average size varying between 110.96 μm and 208.27 μm were obtained. Encapsulation efficiency reached 93.11% at a 1.25% biopolymer concentration. The swelling study showed a swelling rate reaching 29.8% in the gastric medium (pH 1.2) and 360% in the intestinal medium (pH 6.8). The drug release studies showed complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics.

Oil Cakes of Essential Oil Plants as a Source of Prebiotics for Poultry Production

The oil cakes of essential oil plants were screened for prebiotic properties for further development of prebiotic feeds for livestock animals based on these essential oil plants’ extracts. For screening, a microbiota model of the chicken cecum, which was created on the basis of an artificial intestinal medium, was used. This model renders it possible to simulate conditions close to intestinal ones. Oligofructose, inulin, β-glucan, psyllium seeds, and apple fiber at a concentration of 0.5% were used as substances with known prebiotic properties. The oil cake concentration was 0.5%, 1%, 2%, and 4%. The direct antimicrobial effect of the cakes on intestinal bacteria was also investigated. The ability of the cakes to stimulate a decrease in the pH level by Lactobacillus was studied under conditions close to intestinal ones. It was shown that the cakes of big seed false flax (Camelina sativa), brown mustard (Brassica juncea), and spicate lavender (Lavandula angustifolia) exhibit prebiotic properties in relation to the microbiome of chickens in model experiments. They enhance the acid-forming properties of lactic acid bacteria, thereby lowering the pH of the medium. This leads to a decrease in the number of Enterococcus, Escherichia coli, and lactose-positive bacteria, as well as a complete suppression of Proteus. The optimal oil cake concentrations are 1% and 2%. These oil cakes are promising sources of prebiotics for the development of prebiotic feed for agriculture.

O/W Pickering emulsion stabilized by magnesium carbonate particles for drug delivery systems

This study investigates the formulation of surfactant-free Pickering emulsions that release a drug at a specific pH to improve its oral bioavailability. The stabilizing particles composed of magnesium carbonate particles. Pickering oil-in-water emulsions stabilized with magnesium carbonate particles and encapsulating a hydrophobic drug model (ibuprofen) were formulated using a high-energy process with rotor-stator turbo mixer (IKA® T25 digital ultra-Turrax). The experimental approach explored the impact of all formulation parameters, dispersed phase and amount of magnesium carbonate particles on the physicochemical properties of Pickering emulsions. The O/W Pickering emulsion was characterized by a methylene blue test, pH and conductivity measurements, and droplet size determination. In addition, Pickering emulsions stabilized by magnesium carbonate particles have the advantage of being destabilized in acidic medium leading to the release of the active principle via the droplets. The acidic medium release study (pH equal to 1.2) showed ibuprofen release as a function of initial droplet loading and saturation concentration. In the simulated intestinal medium at pH equal to 6.8, we found a better release of ibuprofen from emulsions that already had saturation in an acid medium. Thus, the interest of these Pickering emulsions lies on the fact that their non-toxicity and magnesium carbonate particles allow destabilization of the emulsions and release of the drug. These emulsions not only protect patients from the side effects of acid-based drugs, but also contribute to increase the bioavailability of these acidic drugs.&#x0D; Keywords: emulsion -Pickering-magnesium carbonate- ibuprofen-oral bioavailability

Titanate nanotubes as an efficient oral detoxifying agent against drug overdose: application in rat acetaminophen poisoning.

Voluntary drug intoxication is mainly due to drug overdose or the interaction of several drugs. Coma and its associated complications such as hypoventilation, aspiration pneumopathy, and heart rhythm disorders are the main hallmarks of drug intoxication. Conventional detoxification treatments, including gastric lavage or vomiting, administration of ipecac or activated charcoal (CH), and the use of antidotes, have proven to be inefficient and are generally associated with severe adverse effects. To overcome these limitations, titanate nanotubes (TiNTs) are proposed as an efficient emerging detoxifying agent because of their tubular shape and high adsorption capacity. In the present study, the detoxifying ability of TiNTs was evaluated on paracetamol (PR)-intoxicated rats. Results indicate that the loading ability of PR into TiNTs (70%) was significantly higher than that recorded for CH (38.6%). In simulated intestinal medium, TiNTs showed a controlled drug release of less than 10% after 72 h of incubation. In PR-intoxicated rats, TiNTs treatment resulted in a 64% decrease of PR after 4 h of poisoning versus 40% for CH. Concomitantly, TiNTs efficiently reduced PR absorption by 90% after 24 h of poisoning, attenuated the elevated levels of biochemical markers (i.e., alanine aminotransferase, aspartate aminotransferase, creatinine, and TNF-α) and mitigated oxidative stress by increasing the activity of superoxide dismutase and reducing the oxidized glutathione/total glutathione ratio, suggesting a histoprotective effect of TiNTs against paracetamol-induced toxicity in rats. In addition to their safety and high stability in the entire gastro-intestinal tract, biodistribution analysis revealed that TiNTs exhibited low intestinal absorption owing to their large cluster size of compact aggregate nanomaterials across the intestinal villi hindering the absorption of paracetamol. Collectively, these data provide a new and promising solution for in vivo detoxification. TiNTs are expected to have great potential for the treatment of voluntary and accidental intoxication in emergency care.