Simulated Intestinal Media Research Articles

Synthesis, Characterization, and Stability Optimization of Ibuprofen Cocrystals eEploying Various Hydrophilic Polymers.

Cocrystals are an efficient way for the delivery of low soluble drugs but when dissolved they rapidly disproportionate. To formulate the cocrystals in tablets, cocrystals must be stabilized. In this study ibuprofen-nicotinamide (IBU-NIC) cocrystals were synthesized initially by slow solvent evaporation and for bulk production by fast solvent evaporation techniques. The cocrystals were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectrophotometer (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The ibuprofen cocrystals showed greater solubility compared to the parent drug. Intrinsic dissolution data was utilized for efficacious screening of tablet formulations. Using hydrophilic polymers at a ratio of 6:1 (polymer to IBU-NIC cocrystal ratio), hydroxypropyl methylcellulose (F1), polyvinylpyrrolidone (PVP) K-30 (F2) and PVP K-90 (F3), three tablet formulations were prepared that stabilized cocrystals during dissolution. The drug release profiles after 60 minutes from formulations F1 (92.30), F2 (98.54), F3 (99.88) were all higher compared to the marketed brand BRUFEN® F, (79.61%) in a simulated intestinal media (p<0.001). Significant increase in the dissolution rate of cocrystal was observed with no phase change in all formulations.

Abstract PO1-05-08: Enhanced ER+ tumor growth inhibition of fulvestrant from effective oral delivery yielding elevated plasma concentrations

Abstract Fulvestrant has been a backbone of endocrine therapy (ET) for ER+/HER2- metastatic breast cancer (mBC) for over 20 years due to its nanomolar potency, purely antagonistic behavior, and well-tolerated adverse event (AE) profile. It remains the only selective estrogen receptor degrader (SERD) approved in ER+/HER2- mBC regardless of ESR1 mutation status. While ESR1 mutations reduce fulvestrant binding affinity, they do not implicitly lead to acquired resistance as with aromatase inhibitors (AIs) and can be overcome by increasing exposure.1 Further, preclinical evidence suggests that higher exposure to fulvestrant correlates with higher efficacy in rodents.2 Unfortunately, fulvestrant is currently delivered at its maximum feasible dose due to its poor solubility and a lack of effective drug delivery technologies. In response, several novel oral SERDs have been brought into clinical development to improve upon the efficacy of fulvestrant. However, multiple have failed to prove superior to fulvestrant in its intramuscular (IM) injection formulation and improvements from elacestrant (EMERALD) and camizestrant (SERENA-2) are largely attributed to patients with ESR1 mutations after prior ETs. Therefore, enabling higher exposure of fulvestrant could prolong progression-free survival and improve quality of life for ET-naïve mBC patients and those that have progressed on ETs. VeraMorph has leveraged a proprietary oral drug delivery technology to overcome the limitations of fulvestrant’s poor solubility and potentially help mitigate acquired resistance by improving exposure via daily oral dosing. The oral dosages, which consist of a novel polymer-based soft gummy, stabilize fulvestrant in simulated intestinal media up to 5 mg/mL without influencing fulvestrant permeability or causing cytotoxic effects. Pharmacokinetic (PK) studies of oral fulvestrant in rodents have demonstrated maximum plasma concentrations up to 450 ng/mL, a level roughly 20 times that of the average exposure from the monthly IM formulation in clinical settings. PK studies also demonstrated that oral exposure increased with a roughly dose-proportional relationship, with a reduction in AUC from day 1 to day 8 upon repeat dosing. In a cell-derived xenograft (CDX) study utilizing ER+ MCF-7 tumors implanted in athymic nude mice, once daily dosing via oral gavage of oral fulvestrant at 125 mg/kg was able to achieve a statistically significant 55% reduction in tumor growth by day 42 relative to a 50 mg/kg dose of the IM formulation delivered subcutaneously once per week, which was determined to create an equivalent exposure to the monthly IM human dose in separate studies. Oral fulvestrant yielded no observed adverse effects up to 125 mg/kg in both the 42-day CDX study in mice or an 8-day safety study in rats. Further, onset of action and acquired resistance are being tested by monitoring cell viability (via the MTT assay) with MCF-7 cells exposed to time profiles of fulvestrant exposure resembling oral and monthly intramuscular delivery. The study demonstrated that oral dosing reaches minimal cell viability 1-2 weeks faster than IM dosing. Also, preliminary data suggests that the onset of acquired resistance (as demonstrated by a resumption of cell growth) may occur faster from the steady exposure of IM dosing relative to the modulation of daily oral dosing. These results suggest that oral fulvestrant has the potential to finally realize the full potential of fulvestrant as an effective ET for metastatic breast cancer with a well-tolerated AE profile, enhanced efficacy, and reduced susceptibility to acquired resistance with applicability across all mBC patients. 1 Brett JO, Spring LM, Bardia A, Wander SA (2021) Breast Cancer Research, 23(1):1–15. 2 Wardell SE, et. al. (2020) Breast Cancer Research and Treatment, 179(1):67–77. Citation Format: Doug Godfrin, Matthew Butchbach. Enhanced ER+ tumor growth inhibition of fulvestrant from effective oral delivery yielding elevated plasma concentrations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-08.

Synthesis and evaluation of amylose-mefenamic acid conjugates as colon-targeting prodrugs.

Aim: Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Materials & methods: Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Results: Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Conclusion: Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.

Supporting food effect prediction using biorelevant small scale in vitro solubility approaches

Thisstudy applies biorelevant fasted and fed simulated intestinal media (SIM) to comparethe solubility of griseofulvin, ibuprofen, and dipyridamole to investigate theprediction of food effects. These media cover over 90% of the human intestinalfluid variation in each state providing a comprehensive solubility range invitro. The results highlight that ibuprofen is unaffected by food but dipyridamoleand griseofulvin show an increased solubility in the fed state, suggesting positivefood effects in line with in vivo literature data. Drugs with solubility limitedabsorbable dose (SLAD) lower or close to the oral dose are more likely to presenta food effect, thus SLAD analysis could aid the prediction of food effects. Thisapproach may be applied in early drug development as a preliminary predictiontool.

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.

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.

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.

Targeted delivery of fenamates with aminated starch.

Aim: To develop controlled-release tablets based on aminated starch. Materials & methods: Aminated starch was characterized with Fourier transform infraredand x-ray diffraction. Thermogravimetric analysis confirmed the preferential oxidation of crystalline region of starch. Results: The tablets achieved an initial fast release of fenamates, which slows down after 12h. Drug release was not completed in the simulated intestinal media, which may be due to the stability of imine bond in aminated starch at weakly acidic pH. Drug release was completed in simulated acidic media due to the hydrolysis of imine functionality at strongly acidic pH. Conclusion: Aminated starch with an imine functionality may serve as intestinetargeted, controlled drug-delivery system. Mucoadhesive potential of tablets further supports this observation.

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.

Preparation and optimization of tetraethyl orthosilicate cross-linked chitosan-guar gum-poly(vinyl alcohol) composites reinforced with montmorillonite for sustained release of sitagliptin

Development of efficient drug carriers has become an integral part of advanced drug delivery systems. This work aims at developing composites by adopting an economically viable method for sustained release of anti-diabetic drug sitagliptin — a potent and selective dipeptidyl peptidase-IV inhibitor. To combat the harsh environment of gastrointestinal tract, the composite (F13) was prepared using biodegradable polymers namely chitosan, guar gum and poly(vinyl alcohol) with montmorillonite clay as nano-filler and tetraethyl orthosilicate as the cross linker. The composites were characterized using FT-IR, XRD, DSC and SEM techniques. Physical properties such as thickness, swelling capacity, folding endurance and water solubility were studied. In vitro analysis of composites (F17, F19 and F20) in simulated gastric medium showed <14 % cumulative release in 2 h while a sustained release was observed in simulated intestinal medium. Drug release kinetics was investigated using five mathematical models namely zero order, first order, Higuchi, Hixon-Crowell and Korsemeyer-Peppas wherein the latter was the best fit model (R2, 0.969). Antimicrobial studies of drug free composite (F13) revealed good activity against bacteria as well as fungi. The results implied that the composites were pH sensitive and could serve as a potential choice for sustained release of drugs.

Porous Silica as Drug Carrier for Controlled Delivery of Sulfasalazine: The Effect of Alginate-N, O-Carboxymethyl Chitosan Gel Coating and Amine Functionalization.

The necessity of colon-specific drug delivery systems has been well recognized. Porous silica (PSi) coated with a pH-sensitive, biocompatible, and biodegradable polymer can be useful in colon delivery. In this study, porous silica was synthesized and sulfasalazine was loaded into it to investigate the release rate in a simulated intestinal media. The media was kept at 37°C and pH 6.8 and 7.4, and subjected to continuous ultrasonic waves to simulate body fluid flow. Aqueous alginate and N, O-Carboxymethyl chitosan (NOCC) solutions, with a distinct composition (3% W/V) in different ratios, were prepared and coated on pressed porous silica disks. Porous silica (PSi) was also functionalized by aminopropyltrimethoxysilane grafting and was studied as a potential carrier for the controlled drug release of sulfasalazine. The release was studied in simulated gastric and intestinal media and results show that no burst release occurred in both coated and functionalized samples and the swelling degree of coats at basic and neutral media decreased by the presence of alginate in the network. It is concluded that the coat with a 50:50 ratio can release the colon drugs in 24h at a suitable rate. It is also envisioned that functionalization was a factor boosting drug uptake, however, the release rate was lower in the functionalized samples. This study opens the gates to new ideas for the potential safe and localized delivery of sulfasalazine.

Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant

Self-nanoemulsifying drug delivery systems (SNEDDS) are most commonly used lipid-based drug delivery systems for bioavailability enhancement. Mostly SNEDDS contains high concentrations of synthetic surfactants which may result in gastric irritation and cause toxicity. In this study, Rhamnolipid, a biosurfactant, is utilized as a cosurfactant to minimize the quantity of synthetic surfactant in SNEDDS formulation. Two sets of SNEDDS formulations comprising of medium-chain (MC) or long-chain (LC) glycerides, Kolliphor ® RH40 (KOL) and Rhamnolipid (RL) were produced using a D-optimal design in MODDE software. The monodispersed SNEDDS preconcentrates were further characterized by utilizing dynamic light scattering (at pH 2.5 & 6.5), cryogenic transmission electron microscopy, thermodynamic stability, in-vitro lipid digestion, and viscosity measurements. All MC-SNEDDS preconcentrates were not homogenous and considered unstable, while LC-SNEDDS were homogenous and produced nanoemulsions with droplet sizes ranging from 21 to 336 nm. LC-SNEDDS formulations containing RL produced smaller droplet sizes when dispersed in simulated intestinal media while droplet size slightly increased in the simulated gastric fluid which suggested that RL reduces droplet size more efficiently at higher pH. The zeta potential of nanoemulsion produced by dispersion of LC-SNEDDS containing RL was decreased at low pH. Thermodynamic stability studies have shown that all selected preconcentrates were stable. During in vitro lipolysis, only 24–34% of formulations were enzymatically digested, and at higher concentrations of RL, low number of fatty acids was released. Based on the results of dynamic viscosity studies, all the formulations showed non-Newtonian properties and were suitable for the capsule filling process. During cytotoxicity studies, LC-SNEDDS formulation and RL cosurfactant were well-tolerable at doses normally administered to human. In conclusion, this study demonstrated that LC-SNEDDS comprising RL as cosurfactant are favorable formulations when reduction in the amount of synthetic surfactant is desirable and RL also possibly helps to alter the digestion rate.

Solid Lipid Microparticles as leaching free, slow-release encapsulation system for Methionine in aquaculture

The enrichment of the fish feeds with the essential amino acids like methionine is a common strategy in Aquaculture. Leaching of the amino acids in the water environment and rapid absorption from the Gastro-Intestinal tract are some issues with the free amino acids supplementation strategy. The study aimed to investigate the use of Solid Lipid Microparticles as microencapsulation system for an essential amino acid, methionine. Solid Lipid Microparticles (SLMs) of two lipids, Trimyristin (TM) and Tristearin (TS) were fabricated using a melt emulsification method to encapsulate methionine and compared for their leaching protection and release characteristics in vitro and in vivo. Leaching study performed in the simulated water environment showed that the microparticles were leaching free. In simulated Gastro-Intestinal medias, release was minimal in the gastric media for both systems, while Trimyristin based microparticles showed better release in the simulated intestinal media than Tristearin based microparticles. Oral delivery study in Tilapia by mixing SLMs with the feed showed that the encapsulated methionine can provide slow release compared to the free methionine. Among the two lipids, Trimyristin based SLMs were found to be better digested by the fish. The encapsulation of methionine in lipids can be a suitable alternative for traditional free supplementation strategy for preventing leaching losses and better absorption characteristics for enhanced utilization by the fish.

Polysaccharides-based delivery system for efficient encapsulation and controlled release of food-derived active peptides

A polysaccharides-based delivery system was designed to encapsulate and control the release of peanut peptide (PP). The PP-loaded polyelectrolyte complex (TMC-PP-SA) was fabricated based on the electrostatic self-assembly between n-trimethy chitosan (TMC) and sodium alginate (SA). The complex exhibited uniform spherical morphology, satisfactory stability and high encapsulation efficiency. In vitro release behavior indicated that TMC-PP-SA polyelectrolyte complex could inhibit the release of PP at simulated gastric medium and enhance the release of PP at simulated intestinal medium. Moreover, the antioxidant activity of PP after encapsulation was significantly improved compared with that of directly digested PP. Ex vivo intestinal permeation study confirmed that about 41.76 ± 1.43% PP in TMC-PP-SA could be absorbed in the intestinal. The cytotoxicity measurement indicated that the fabricated TMC-PP-SA polyelectrolyte complex was biocompatible and nontoxic. Therefore, these results indicated that the polysaccharides-based delivery system had great potential in protecting active peptides from degradation and facilitating their absorption.

Red Fluorescence of Eu3+-Doped ZnAl-LDH Response to Intercalation and Release of Ibuprofen.

A drug delivery system with identification function is attractive and important. For this reason, the red fluorescence of Eu3+-doped ZnAl-LDH response to intercalation and release of ibuprofen (IBU) has been studied. X-ray diffraction(XRD) results showed that the basal spacing of the Eu3+-doped ZnAl-LDH varied from 8.85 to 12.04Å after the intercalation of IBU. The release of the IBU from the Eu3+-doped ZnAl-LDH was carried out in simulated intestinal medium (phosphate buffer solutions with pH 7.4 and 37°C), and the releasing behavior of IBU exhibited an initial rapid release followed by a slow release. Moreover, the present delivery system has slower release of drug than those of other LDH-based delivery systems. Interestingly, the intercalation of IBU into the Eu3+-doped ZnAl-LDH obviously reduced the red fluorescence of the Eu3+-doped ZnAl-LDH, whereas the red fluorescence was recovered after the release of IBU. This fluorescent responsiveness may be a favorable signal for detecting the delivery and release of IBU. Therefore, the Eu3+-doped ZnAl-LDH with red fluorescence would be potential application as drug delivery system with identification function because of its cheapness, non-toxicity, good biocompatibility, and little damage to biological tissue.

Flumequine-loaded titanate nanotubes as antibacterial agents for aquaculture farms.

Flumequine (FLUM), a quinolone-derived antibiotic is one of the most prescribed drugs in aquaculture farms. However, its intensive use becomes worrisome because of its environmental risks and the emergence of FLUM-resistant bacteria. To overcome these problems we propose in this study the encapsulation and the delivery of FLUM by titanate nanotubes (TiNTs). Optimal FLUM loading was reached by suspending the dehydrated powder nanomaterials (FLUM : TiNTs ratio = 1 : 5) in ethanol. The drug entrapment efficiency was calculated to be 80% approximately with a sustained release in PBS at 37 °C up to 5 days. Then FLUM@TiNTs was evaluated for both its in vitro drug release and antimicrobial activity against Escherichia coli (E. coli). Spectacularly high antibacterial activity compared to those of free FLUM antibiotic was obtained confirming the efficiency of TiNTs to protect FLUM from rapid degradation and transformation within bacteria improving thereby its antibacterial effect. Indeed FLUM@TiNTs was efficient to decrease gradually the bacterial viability to reach ≈5% after 5 days versus ≈75% with free FLUM. Finally, the ex vivo permeation experiments on sea bass (Dicentrachus labrax) intestine shows that TiNTs act to increase the intestinal permeation of FLUM during the experiment. Indeed the encapsulated FLUM flux increased 12 fold (1.46 μg cm2 h−1) compared to the free antibiotic (0.18 μg cm2 h−1). Thanks to its physical properties (diameter 10 nm, tubular shape…) and its high stability in the simulated intestinal medium, TiNTs are easy internalized by enterocytes, thus involving an endocytosis mechanism, and then improve intestinal permeation of FLUM. Taken together, FLUM@TiNTs hold potential as an effective approach for enhancing the antimicrobial activity of FLUM and pave the way not only for future pharmacokinetic studies in the treatment and targeting of fish infections but also for instating of novel strategies that overcome the challenges associated with the abusive use of antibiotics in fish farming.

Sustainable Stabilizer-Free Nanoparticle Formulations of Valsartan Using Eudragit® RLPO.

The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit® RLPO using an emulsion–solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticles, resulting in a monodisperse colloid system ranging in size between 148 nm and 162 nm. Additionally, a high encapsulation efficiency (96.4%) was observed. However, due to the quaternary ammonium groups of Eudragit® RLPO, the stabilization of the dispersion could be achieved in the absence of PVA as well. The nanoparticles were reduced in size (by 22%) and exhibited similar encapsulation efficiencies (96.4%). This more cost-effective and sustainable production method reduces the use of excipients and their expected emission into the environment. The drug release from valsartan-loaded nanoparticles was evaluated in a two-stage biorelevant dissolution set-up, leading to the rapid dissolution of valsartan in a simulated intestinal medium. In silico simulations using a model validated previously indicate a potential dose reduction of 60–70% compared to existing drug products. This further reduces the expected emission of the ecotoxic compound into the environment.